ALTE04N1 Activated: 10/18/2004 Version Date:

Transcription

ALTE04N1
Activated:
Closed:
10/18/2004
Version Date:
Amendment
04/14/2010
#4
CHILDREN'S ONCOLOGY GROUP
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HEALTH-RELATED OUTCOMES FOR HODGKIN DISEASE SURVIVORS
A Limited Non-Therapeutic Study
Children’s Hospital Regional Medical Center –Coordinating Center
The Fred Hutchinson Cancer Research Center
University of Minnesota
University of California Los Angeles
Children’s Hospital of Philadelphia
Columbia University
Rhode Island Hospital
Memorial Sloan Kettering Cancer Center
Rochester University
St. Jude Children’s Research Hospital
Stanford University
Texas Children’s Hospital, Baylor University
Hackensack University Medical Center (Tomorrow Children's Med Ctr)
Cincinnati Children’s Hospital Medical Center
University of Chicago
University of Texas Southwestern
Vanderbilt Children’s Hospital
Yale University
THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, AND SHOULD NOT BE COPIED, REDISTRIBUTED OR USED FOR
ANY OTHER PURPOSE.
STUDY CHAIR
Debra L. Friedman, MD, MS
Associate Professor of Pediatrics
E. Bronson Ingram Chair in Pediatric Oncology
Division Director, Pediatric Oncology/Hematology
Co- Leader, Cancer Epidemiology, Control and Prevention Program
Vanderbilt-Ingram Cancer Center
397 Preston Research Building
2220 Pierce Ave.
Nashville, TN 37232
Phone: 615-322-9397
Fax: 615-936-1767
Email: [email protected]
Statistical and Data Center Contact: http://members.childrensoncologygroup.org
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TABLE OF CONTENTS
SECTION
STUDY COMMITTEE
PAGE
3
ABSTRACT
5
EXPERIMENTAL DESIGN SCHEMA
6
1.0
SPECIFIC AIMS
8
2.0
BACKGROUND AND RATIONALE
2.1
Introduction
2.2
Pediatric Hodgkin disease treatment: Paradigm shift over time
2.3
Late Effects of Hodgkin Disease therapy
2.4
Screening Hodgkin disease survivors for adverse health-related outcomes
8
8
8
9
11
3.0
ENROLLMENT PROCEDURES AND ELIGIBILITY CRITERIA
3.1
Study Enrollment
3.2
Patient Eligibility Criteria
11
11
12
4.0
MATERIALS AND METHODS
4.1
Required Procedures
4.2
Additional Data
4.3
Specimen Collection and Submission
4.4
Laboratory Analysis
13
13
16
16
16
5.0
STATISTICAL CONSIDERATIONS
5.1
Statistical Design
5.2
Accrual (and Expected Duration of Accrual)
5.3
Statistical Analysis Methods
16
16
16
17
REFERENCES
21
SAMPLE INFORMED CONSENT
28
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THIS PROTOCOL IS FOR RESEARCH PURPOSES ONLY, SEE PAGE 1 FOR USAGE POLICY
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STUDY COMMITTEE
STUDY CHAIR
Debra Friedman, MD,MS
Associate Professor of Pediatrics
Vanderbilt Children's Hospital
Ingram Cancer Center
397 Preston Research Building
2220 Pierce Ave.
Nashville, TN 37203
Phone: (615) 332-93974
Fax: (615) 936-1767
E-mail: [email protected]
STUDY COMMITTEE MEMBERS
Wendy Hobbie
Nurse
Children’s Hospital of Philadelphia
Oncology
34th & Civic Center Blvd.
Philadelphia, PA 19104
Phone: (215) 590-4562
Fax: (215) 590-4183
STUDY VICE CHAIR
Cindy Schwartz, MD
Hematology/Oncology
Rhode Island Hospital
Pediatrics/Hematology/Oncology
593 Eddy Street
Providence, RI 02903
Phone: (401) 444-5171
Fax: (401) 444-8845
Kathy Ruble
Nurse
Johns Hopkins Hospital
Pediatric Oncology
6215 Leithwalk
Baltimore, MD 21239
Phone: (410) 955-2457
Fax: (410) 955-0028
E-mail: rubleka@jhmi
STUDY STATISTICIAN
Lu Chen, Ph.D
Children's Oncology Group - Operations Center
Statistics
440 E. Huntington Drive; 4th Floor
Arcadia, CA 91006
Phone: (626) 241-1520
Fax: (626) 445-4334
Barbara “Bobbi” Stansfeld, CRA III
Clinical Research Associate (CRA)
Seattle Children's Hospital
1900 Ninth Ave.
Mailstop C9S-9C
Seattle, WA 98101
Phone: (206) 884-1018
Fax: (206) 729-3062
Melissa Maria Hudson, MD
Pediatric Oncologist
St. Jude Children's Research Hospital Memphis
Hematology/Oncology
262 Danny Thomas Place
MS 735
Memphis, TN 38105
Phone: (901) 595-3445
Fax: (901) 595-3045
Louis S. Constine, MD
Radiation Oncology
University of Rochester Medical Center
601 Elmwood Avenue
Box 647
Rochester, NY 14642
Phone: (585) 275-5622
Fax: (585) 275-1531
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Doojduen Villaluna, MS
Statistics
Group Operations Center
Arcadia, CA 91006
Phone: (626) 241-1525
Fax: (626) 445-4334
RESEARCH COORDINATOR
Smita G. Subramanian, MS
Statistics & Data Center
440 E. Huntington Drive
Arcadia, CA 91006
Phone: (626) 241-1623
Fax: (626) 445-4334
Kevin Charles Oeffinger, MD
Pediatric Oncologist
Memorial Sloan-Kettering Cancer Center
Pediatrics
1275 York Avenue
Box 396
New York, NY 10065
Phone: (212) 639-8469
Fax: (212) 717-3239
PROTOCOL COORDINATOR
Lanie Lindenfeld, MA
Group Operations Center
Arcadia, CA 91006
Phone: (626) 241-1575
Fax: (626) 447-4293
Lonnie Zeltzer, MD
UCLA David Geffen School of Medicine
Department of Pediatrics--UCLA
10833 Le Conte Avenue
Los Angeles, CA 90095-1752
Phone: (310) 825-0731
Fax: (310) 794-2104
For Group Operations (GOC) and
Research Data Center (RDC) contacts see:
http://members.childrensoncologygroup.org
Telephone:
(626) 447-0064
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The Children's Oncology Group has received a Ce
rtificate of Confidentiality from the federal
government, which will help us protect the privacy of our research subjects. The Certificate protects
against the involuntary release of inform ation about y our subjects collected during the course of our
covered studies. The researchers involved in the studi es cannot be forced to disclose the identity or any
information collected in the study in any legal proceedings at the federal, state, or local level, regardless
of whether they are crim inal, administrative, or le gislative proceedings. However, the subject or the
researcher may choose to voluntarily disclose the protected information under certain circumstances. For
example, if the subject or his/her guardian requests the release of inform ation in writing, the Certificate
does not protect against that voluntary disclosure. Furthermore, federal agencies may review our records
under limited circumstances, such as a DHHS request for information for an audit or program evaluation
or an FDA request under the Food, Drug and Cosmetics Act.
ABSTRACT
Survival from pediatric Hodgkin disease now exceeds 85%, resulting in a growing cohort of
survivors
who are at risk for adverse long-term health-related outcomes. With changes in multi-modality therapy
over time, the prevalence, incidence and spectrum of such outcomes is likely to change. While there are
data on long-term adverse health-related outcom es for patients treated in the 1960’s through the early
1980’s, there is little systematically collected information regarding similar outcomes for patients treated
in the m ore contemporary era from 1987 to the present. This latter period was notable for therapeutic
changes that included reductions in the use of alkylating agents, anthracy clines and radiotherapy ,
specifically to decrease adverse long-term outcomes in areas of cardiopulmonary, endocrine, reproductive
and psychological health and to decrease the inciden ce of secondary malignant neoplasms. Current late
effects screening criteria are largely based on studi es of Hodgkin disease survivors treated in the earlier
era of chemotherapy and radiotherapy, and may not be applicable to more contemporarily treated patients.
The spectrum and incidence of late effects experienced by these patients can inform us with respect to the
design of future risk-adapted therapeutic trials.
The study will utilize two unique resources in a collaborative m anner: The Childhood Cancer Survivor Study
(CCSS), an NCI-supported 25-institution cohort study tracking the outcom es of 14,000 childhood cancer
survivors, and the Children’s Oncology Group. With de dicated investigators in long-term outcomes, and a
clinical infrastructure that supports risk-directed clinical studies, in a group of Hodgkin disease survivors
treated on or in parallel to cooperative group and consortium studies after 1986, we will seek to evaluate the
health-related outcomes of Hodgkin disease survivors treated with risk-adapted therapy. This cohort study will
evaluate by 1) patient self-report and 2) clinical
evaluation and m edical record review, the incidence,
prevalence and spectrum of the following targeted a dverse long-term outcomes. In eligible Hodgkin disease
survivors, diagnosed from 1987 until the present, who are at least 5-years from diagnosis, treated or currently
followed at any one of the participating institutions we will:
1. Conduct risk-based clinical evaluations and identify selected phy siologic and psy chologic long-term
sequelae of treatment. The spectrum of adverse out comes will be characterized and the cum ulative
incidence will be determined.
2. Compare the self-reported selected phy siologic and psychologic long-term sequelae of treatment
from this contem porary cohort with the Hodgkin disease survivors from
the CCSS treated
between 1976 and 1986, with data collected at a comparable point following diagnosis.
3. Compare and validate the self-reported phy siologic and psy chologic long-term sequelae of
treatment with those determined by clinical evaluation and m edical record review in the
contemporary cohort, and validate selected phy siologic complications with medical review in the
CCSS cohort.
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EXPERIMENTAL DESIGN SCHEMA
1. All COG center study participants
Completion of
CCSS baseline
questionnaire
Consent and
enrollment on
study
Survivors return to a
treating or participating
institutions or PMD for
clinical evaluation
Characterization of
prevalence, spectrum and
cumulative incidence of
cardiac, pulmonary,
gonadal, thyroid,
psychosocial outcomes and
SMN
Medical record review
and risk-based clinical
evaluation
2. Data to be obtained from CCSS participants treated 1976 –1986 only
Review of replies for
targeted outcomes
from CCSS baseline
questionnaire already
completed
Medical record
review for
selected positive
responses
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3.Comparsion of outcomes
Contemporary cohort selfreport data
Contemporary cohort data from medical
records and clinical evaluation
1.
Compare self-reported
cardiac, pulmonary, gonadal,
thyroid outcomes, SMN and
BSI at same time point from
diagnosis
CCSS cohort self report data
CCSS cohort medical record review
3.
Compare self-reported cardiac, pulmonary, gonadal, thyroid,
complications and SMN with medical record review
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1.0
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SPECIFIC AIMS
1.1
To determine the cumulative incidence and characterize the spectrum of targeted adverse physiologic and
psychosocial outcomes, using self -report and clinical evaluation.
1.2
To compare the cum ulative incidence and spectru m of self-reported adverse outcomes with Hodgkin
disease survivors from the CCSS, with data collected at a comparable time period following diagnosis
1.3
To compare self-reported health-related outcom es with t hose detected by clinical evaluation and m edical
record review in the contemporary cohort, and by medical record review in the CCSS cohort.
2.0
BACKGROUND AND RATIONALE
2.1
Introduction
The very therapy that has resulted in im proved long-term survival in Hodgkin disease can also lead to longterm morbidity and mortality. Specifically, survivors of Hodgkin disease are subject to excess risk of
cardiopulmonary dysfunction, thyroid disease, infer tility, second malignancies and im paired psychosocial
functioning and general health-related quality of life [1]. Priority areas of research for this and other survivor
cohorts include descriptive and analy tic epidemiologic studies to 1) define incidence of adverse phy siologic
and psychologic long-term sequelae that may be altered by changes in therapy over time; 2) develop standards
for best practices for screening and
early intervention to ameliorate these late effects and 3) develop
preventive strategies to avoid these late effects [2-4].
Research to date has focused on ther apeutic advances, physiologic or psychologic outcomes, often targeting a
single research domain. In addition, outcom es studies have largely examined late effects of therapies of the
1960s through the early 1980s. There has been a paucity of similar research for patients treated from 1987
onward, when risk-adapted studies were conducted to re duce long-term morbidity and mortality. The lack of
such research has many implications.
Cancer survivors are often unaware of potential long-term health problem s for which they may be at risk.
Conversely, health-care providers are unable to provide a quantitative estimate of that risk, especially for those
who are now 5 to 15 years from diagnosis. Current late effects screening guidelines are largely based on longterm toxicities experienced by Hodgkin disease survivors treated with different therapies in the 1960’s through
the early 1980’s. These guidelines may not be applicable to more contemporarily treated patients, who may be
subject to inappropriate screening, if indeed, the risk profile has changed. Moreover, the quality of their lives
may be compromised by the concerns engendered in them by currently recommended screening guidelines. In
an era of health cost containment, the cost-benefit ratio remains unclear.
2.2
Pediatric Hodgkin disease treatment: Paradigm shift over time
Over the past 25 y ears, there has been a paradigm shift in the approach to pediatric Hodgkin disease, largely
due to the recognition that long-term toxicity from treatment was enhanced in children and adolescents, and
may have adverse outcomes that exist and potentially worsen over a longer life span. As a result, therapeutic
trials have evolved over tim e from those with cure as the primary aim to those with dual aim s of maximum
cure with minimum long-term toxicity.
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Donaldson first introduced the concept of combined modality therapy for pediatric patients using the
MOPP backbone and low-dose radiation therapy
[5]. To decrease the dose
of mechlorethamine,
subsequent therapies then built upon the MOPP backbone in the 1980’s, such as the MOPP/ABVD hybrid
therapies [6-10]. Starting in 1987, pediatric cooperative treatment groups further developed risk-adapted
therapies designed to reduce late effects with reducti ons in therapy based on a combination of rapid early
response, risk stratum and gender-specific late effects. These included reductions in alkylating agent dose
and use, radiotherapy use and dose and anthracycline dose [11-23].
2.3
Late Effects of Hodgkin Disease therapy
2.3.1 Cardiac toxicity
Survivors of Hodgkin disease are at risk of cardiotoxi city from both radiotherapy and doxorubicin. Risk
factors for doxorubicin-related cardiom yopathy include female sex, cumulative doses greater than 200 300mg/m2, younger age at tim e of exposure and increased time from exposure. Thoracic radiotherapy
further increases this risk, in a dose-dependent manner. Cardiomyopathy rates range widely across studies
from 0.5% to 30 % at 30 y ears, and the spectrum and cumulative incidence has not been docum ented for
contemporary survivors of pediatric Hodgkin disease [ 24-31]. The only published guidelines for
monitoring cardiotoxicity in survivors of childhood can cer are greater than a decade old, reflect risk
conferred by higher doses of anthracy cline combined with higher doses of radiotherapy , and have not
been universally applied [32, 33].
Early mortality from cardiac causes in Hodgkin disease survivors has been prom inent in several studies
[25, 34, 35]. In a recent review, Donaldson and colleagues state that 14% of Hodgkin disease survivors
will die prem aturely from cardiovascular causes [ 36]. Little is known about the clinical spectrum of
nonfatal toxicity, or about the functional or psychosocial implications of this toxicity.
In recognition of these risks, in the recent CCG, POG and PHC studies, we have attem pted to reduce toxicity
with reduction in radiotherapy dose, tailoring of ra diotherapy fields, reduction in doxorubicin dose based on
stage and response to initial therapy , and use of dexr azoxane, (DZR), a chelating agent, shown to prevent
anthracycline-induced cardiotoxicity [16, 20-23, 37-41] . Long-term cardiac outcom es research in patients
treated on these newer risk-adapted studies has been limited by small sample size, inadequate follow-up,
selection bias and the lack of consistent m ethodology for assessing risk. Therefore, findings of little long-term
cardiotoxicity must be viewed with some caution [9, 42, 43].
2.3.2 Pulmonary toxicity
Pulmonary fibrotic disease and abnormal pulmonary diffusion are seen as late com plications, occurring 5
to 20 y ears following thoracic radiotherapy and the use of bleomycin [44-48]. A few pediatric studies,
limited by size and selection bias, have found rat es of 55 – 75% for abnorm al pulmonary diffusion,
although the functional significance of these findings has not been evaluated [ 42, 49, 50]. In the CCSS
cohort, pulmonary disease resulted in excess early mortality, with a standardized mortality ratio (SMR) of
9.2 [35]. A further analy sis of self-reported pulm onary complications in the CCSS revealed statistically
significant associations for lung fibrosis and supplem ental oxygen use with thoracic radiotherapy or
bleomycin exposures [51].
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2.3.3 Thyroid disease
Hypothyroidism is well docum ented in survivors of Hodgkin disease with a peak incidence 3-7 y ears
following treatment. A radiotherapy dose-response re lationship has been dem onstrated [52-54]. The
incidence of other thy roid abnormalities such as hy perthyroidism and thy roid nodules are less well
documented, and thyroid nodules are often not seen until 7 or m ore years post treatm ent [54, 55]. The
largest study of thy roid disease in Hodgkin disease survivors com es from the self-report data of the
CCSS, where 34% of Hodgkin disease patients reported at least one thyroid abnormality [55].
2.3.4 Gonadal toxicity
For males, there is evidence that Hodgkin disease itself m ay result in abnorm ality of sperm number and
function [56, 57]. Spermatogenesis is then highly sensitive to alkylating agents, a mainstay of Hodgkin disease
therapy. Cyclophosphamide causes dam age to sperm atogonia in a dose-dependent m anner. This gonadal
toxicity is enhanced by co-administration of other alkylating agents, such as procarbazine [58-64]. Reduction
of alkylating agent therapy in multiagent protocols has resulted in reduction of the risk for male infertility [19,
59, 61, 62, 65]. The degree and permanency of radiotherapy-induced damage to the male reproductive system
is dose, field, schedule and age dependent [ 66-68]. Some males treated with chem otherapy and radiotherapy
may recover gonadal function after a period of infertility. [69].
While short term follow-up reveals that the m ajority of females have retained norm al menstrual function
[69], later risk of prem ature menopause is of concern. Two large studies of childhood cancer survivors
treated through the 1980’s have shown elevated rates for infertility and elevated relative risks for early
menopause for Hodgkin disease survivors treated with abdominopelvic radiotherapy and alkylating agents
[70, 71]. Mechlorethamine and procarbazine together are the most damaging chemotherapeutic agents to
the gonads. Substitution of cy clophosphamide for mechlorethamine appears to have reduced the risk of
ovarian dysfunction [72]. However, the overall risk and incidence of prem ature menopause is still
unknown, as survivors treated with cyclophosphamide are only now approaching the age where
premature menopause was previously reported with m echlorethamine use. The ovary is also sensitive to
the effects of ionizing radiation, with age and dose effects evident [66, 67, 73].
2.3.5 Second malignant neoplasms
Second malignant neoplasms (SMN) following Hodgkin disease occur m ore frequently than after any
other pediatric cancer, with the exception of hereditary retinoblastoma, where a tumor suppressor gene is
known to play an essential role. Second m alignancies also contribute significantly to early mortality in
survivors of pediatric Hodgkin disease [25, 34, 35, 74] . Follow-up from a num ber of large cohorts
demonstrates a rising incidence and a changing spect rum of second m alignancies with increased elapsed
time from treatment. Within the first 5 to 15 years from diagnosis, leukemia is predominant with a plateau
in incidence seen at 10 to 15 y ears from diagnosis. The risk of solid tumors starts to rise at 7 to 10 y ears
post diagnosis, and continues to rise with incr
eased elapsed tim e from diagnosis, with no plateau
identified. Breast cancer is now the most common second primary malignancy following Hodgkin disease
[75-88].
The increased risk for second prim ary malignancies has been a clear im petus to changes in therapy for
children with Hodgkin disease. Leukem ia risk in Hodgkin disease has been associated with alky lating
agent exposure in a dose-dependent m anner. Mechlorethamine was found to be m ore leukemogenic than
cyclophosphamide [89, 90]. Therefore, in the early 1990’s, mechlorethamine was deleted from pediatric
cooperative group and consortium therapeutic protocols. Exposure to thoracic radiotherapy has been
identified as the major treatment risk factor for breast cancer. Knowledge of this association has, in turn,
lead to a reduction in the doses and fields of thoracic radiotherapy , especially for females [1, 16, 23, 91] .
Due to the longer latency periods for solid tumors, more time has yet to elapse before it can be determined
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that the risk and incidence of
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breast and other solid organ cancers will indeed be reduced by
these
2.3.6 Psychosocial outcomes
Decreased health-related quality of life, increased fatigue, depression and post-traumatic stress are
reported in adult survivors of pediatric Hodgkin disease and other hem atologic malignancies [92-104],
and can m anifest five to twenty years following tr eatment. However, the full spectrum of psy chosocial
outcomes remains largely unknown. Furthermore, the im pact of the changing spectrum of phy siologic
morbidities on psychologic outcome has not been studi ed. The CCSS has published the largest study of
psychological health in pediatric Hodgkin disease. Survi vors were more likely than sibling controls to
report symptoms of depression and som atic distress, with fem ales at higher risk than males. The only
treatment variable that predicted scores indicating depressive symptomatology was exposure to intensive
chemotherapy [97]. These findings will be im portant to re-examine in our contem porary cohort, where,
over time, we have developed shorter, but more dose-intensive regimens for pediatric Hodgkin disease.
2.4
Screening Hodgkin disease survivors for adverse health-related outcomes
Using a thorough review of the literature, as well as the
collective clinical experience of clinicians and
researchers with expertise in long-term health-related outcomes, the COG Late Effects com mittee has
developed late effects screening guidelines to assist surv ivors and health care providers with risk-based longterm follow-up. However, m uch of the literature utilized in that review largely reflects long-term outcomes
from therapies utilized through the early 1980s, which ar e no longer used. Therefore, it is unclear whether
these guidelines reflect changes in therapy over time. The guidelines may recommend excessive screening in
some areas and inadequate screening in others. In the clin ical evaluations that will be conducted in this study ,
we will use these guidelines in a standardized and form alized manner and obtain some exploratory data about
their use in contemporarily treated survivors.
3.0
ENROLLMENT PROCEDURES AND ELIGIBILITY CRITERIA
3.1
Study Enrollment
3.1.1 IRB Approval
Upon receipt of local IRB approval for a COG study , fax the officially signed IRB approval to the Group
Operations Center (GOC) at: (626) 445-6715. The COG IRB Approval Fax Cover Sheet is required to be
faxed with the official approval. A copy of this cover memo can be obtained from the protocol links area
of the COG website. After this approval is recorded by GOC staff, the institution will have access to the
eRDE enrollment screens.
3.1.2 Patient Registration
Prior to study enrollment, all patients m ust have b een registered via the eR DE system into the COG
Cancer Registry (Diagnosis/Registry). The patient re gistration application is available 24 hours a day , 7
days a week. The assigned COG patient identification number will be used to identify the patient in all
future interactions with the COG. If you have problems with registration, please refer to the online help in
the eRDE area of the COG website.
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3.1.3 Study Enrollment
Patients may be enrolled on the study once all eligibility requirements for the study have been met. Study
enrollment is accom plished by going to the Enrollment application in the eRDE sy stem. If y ou have
problems with enrollment, refer to the online help in the Applications area of the COG website.
3.2
Patient Eligibility Criteria
Important note: The eligibility criteria listed below are interpreted literally and cannot be waived
(per COG policy posted 5/11/01).
3.2.1 Case Criteria
Eligibility for participation includes:

Treatment for primary Hodgkin disease at any one of the participating institutions 1987 –
onward, or patients otherwise eligible and cu rrently followed at one of the participating
institutions

Age < 21 years at time of diagnosis

Alive without evidence of disease at time of study entry

At least 5 years from diagnosis at time of study entry

Initial treatment on or in parallel to the following protocols: Children’s Cancer Group
(CCG) 5942, 59704; Pediatric Oncology Group (POG) 8625, 8725, 9226, 9225, 9425,
9426; Pediatric Hodgkin’s Consortium : VAMP, VEPA, VAMP/COP, Stanford V, and
the following institutional protocols: COPP/ABV, COPP/ABVD,
MOPP/ABV,
MOPP/ABVD, ABVD.

Patients treated with radiotherapy alone as initial therapy are not eligible, nor are patients
treated with radiotherapy for initial treatm ent at doses of >30Gy as part of multimodal
therapy

Patients who m eet above criteria and subsequently relapsed, and received additional
therapy, are eligible, provided their initial th erapy consisted of the eligible protocols
above.
3.2.2 Control Criteria
For comparison of outcom es, the self-report data from the COG participants will be com pared with that
previously reported by participants with Hodgkin disease who are pa rticipants in the Childhood Cancer
Survivor Study (CCSS). This will include Hodgkin disease survivors as follows:
 Current enrollment in the CCSS
3.2.3

Diagnosed 1976 – 1986

Completed baseline questionnaire at com parable time points following diagnosis as
contemporary cohort
Regulatory
3.2.3.1
All patients and/or their parents or legal guardians must sign a written informed consent.
3.2.3.2
All institutional, FDA, and NCI requirements for human studies must be met.
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4.0
MATERIALS AND METHODS
4.1
Required Procedures
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4.1.1 Subject ascertainment
All eligible participants will be inv ited to 1) participate in the study and 2) return to their participating
institution for the com plete clinical evaluation. For those desiring participation, but who no longer live
near their institution, they will be provided the contact for the closest participating institution. For those
who wish to participate, but cannot or will not return to any of the participating institutions, the clinical
evaluation can be com pleted by their community health care provider (CHCP). The institutional PI will
work with the survivors to facilitate the clinical evaluation at the treating institution, another participating
institution, or through the community health care provider.
As we are aware that inability or unwillingness to return to one’s treatment center is one of the reasons for
lack of appropriate long-term monitoring for Hodgkin disease survivors, we will collect inform ation on
participating and non-participating eligible survivors as outlined in Table 1 below.
Table 1: Categories of participation
Unable to contact for participation: Lost-to-follow-up despite tracing attempts
Full active refusal
Passive refusal
Participation with clinical evaluation at treating institution with cancer survivorship program
Participation with clinical evaluation at participating institution with cancer survivorship program
Participation with clinical evaluation at CHCP
Due to inability to return to treating or participating institutions with cancer survivorship program
Due to refusal to return to treating or participating institutions with cancer survivorship program
(Reasons for inability or refusal to return to treating or participating institutions will be collected)
Completion of self-report questionnaire with refusal for clinical evaluation
Completion of self- report questionnaire with expressed desire to participate in clinical evaluation but unable due to:
Lack of insurance
CHCP referral required for treating or participating center evaluation and refused
Refusal to return to treating or participating institutions with late effects program and
Do not have CHCP
CHCP refuses to conduct evaluation
4.1.2 Targeted long-term health-related outcomes for study
The targeted outcomes to be investigated in this proposal are:
1.
CARDIAC: Cardiomyopathy, valvular insufficiency, arrhythmia, coronary artery disease,
myocardial infarction, invasive cardiac procedures
2.
PULMONARY: Pulmonary fibrosis, decreased pulmonary diffusion
3.
ENDOCRINE: Hyperthyroidism, hypothyroidism, thyroid nodules
4.
GONADAL: Primary or secondary ovarian failure, azoospermia, oligospermia
5.
SECOND MALIGNANCIES: Secondary leukemia, second primary solid tumors
6.
PSYCHOSOCIAL: Health-related quality of life, sexual quality of life, fatigue, sleep, post
traumatic stress, post traumatic growth, symptoms of depression or somatic distress
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4.1.3
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Specific study required procedures
4.1.3.1 Self report questionnaire
Upon study entry, after signing inform ed consent and release of personal heath inform ation documents,
each participant (or parent, if under 18 y ears of age) will complete the self-report study instrument, based
upon the CCSS Baseline Questionnaire (See Data Form s on COG’ s website) and will return it to the
treating institution in the provided postage-paid mailer. The institution will forward a copy of the consent
and the completed questionnaire to the coordinating center in Seattle.
If participants so desire, the questionnaire can also be completed via telephone interview. This telephone
interview will be conducted by trained interviewers at the Fred Hutchinson Cancer Research Center
(FHCRC) in Seattle, Washington, working in collabor ation with the study chair and the coordinating
center for the study, Children’s Hospital and Regional Medical Center.
If participants wish to com plete the questionnaire by telephone, a m ember of the research team at the
participating institution will get consent from the patient and will complete the “ALTE04N1: Request for
Telephone Administration of HD Patient Questionna ire” and fax to Barbara Stansfeld and
to
Collaborative Data Services at the institution.
Collaborative Data Services
Collaborative Data Services (CDS) is a shared resour ce, physically located in FHCRC Division of Public
Health Sciences (PHS), and is made up of two research support units: the Survey Research Unit and the
Institutional Review Board policies
Programming Unit. All CDS staff receives ongoing training in
including specific modules addressing the Health Insurance Portability and Accountability Act (HIPAA)
privacy and security rules in addition to Human Subjects Training.
The Survey Research Unit specializes in survey design, developm ent, and testing; survey coding,
batching, key entry, and verificati on; and development and processing of optically scanned surveys. It
also offers interviewing by telephone including co mputer-aided telephone interviewing that can be
directly linked to autom ated sample management or random digit dialing software applications. Other
services in this unit include data m
anagement; mail assembly and tracking, and overall project
coordination. The Programming Unit provides software developm ent and programming support for CDS
key-entry, optical scanning, tracking sy stems and te lephone interviewing services, and also for outside
customers.
4.1.3.2 Medical record abstraction
For all participating patients, the institutional prin cipal investigator will be responsible for providing
treatment data (cumulative chemotherapy doses, radiotherapy doses, fields and volumes) to correlate with
health outcomes. In addition to abstraction of treatm ent data, the institutional principal investigator will
abstract the m edical record for any prevalent m edical conditions that fall within the spectrum of the
targeted outcomes (See Data Forms on COG’s website).
4.1.3.3 Clinical evaluation
After completion and return of the CCSS self-report questionnaire, and a m edical record review, all
subjects will receive a single com prehensive risk-based clinical evaluation, with specific exam inations
and studies based upon recom mendations contained within the COG Late Effects Screening Guidelines,
as appropriate for Hodgkin disease, and the participants ’ specific therapeutic exposures. This clinical
evaluation will be recorded on a uniform entry form (See Data Form s on COG’s website). The specific
study are based upon therapeutic exposures and are derived directly from the COG Late Effects Screening
Guidelines [105].
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Specified Clinical Evaluations from COG Late Effects Screening Guidelines
Targeted outcome
Cardiomyopathy
Arrhythmia
Hyperlipidemia
Pulmonary fibrosis
Interstitial pneumonitis
Thyroid function
Thyroid nodule
Female Gonadal evaluation
Male Gonadal evaluation
Therapy-related leukemia
Bladder malignancy
Thyroid cancer
Breast cancer
Gastrointestinal malignancy
General cancer screening
Any psychosocial problem
Associated
exposure
therapeutic
CARDIAC
Doxorubicin, chest radiotherapy
Doxorubicin, chest radiotherapy
Doxorubicin , chest radiotherapy
PULMONARY
Bleomycin, chest radiotherapy
Neck radiotherapy
Neck radiotherapy
ENDOCRINE
GONADAL
Cyclophosphamide, Mechlorethamine
Dacarbazine, Procarbazine
Pelvic radiotherapy
Dacarbazine, Procarbazine
Pelvic radiotherapy
Screening tests (in addition to routine health
history and physical examination
Echocardiogram
Electrocardiogram
Fasting lipid profile
Pulmonary function tests
Chest X Ray
TSH and Free T4
Palpation of thyroid gland; Imaging if abnormal
For patients age 11 years or older:
LH, FSH, estradiol
For patients who have failed to proceed through puberty
Gynecology or reproductive endocrinology consultation for
consideration of hormonal replacement therapy
For post-pubertal patients who have unsuccessfully tried to
become pregnant, who have irregular menses, signs or
symptoms of premature menopause:
Gynecology or reproductive endocrinology consultation for,
infertility consultation
For patients age 11 years or older:
Testicular volume by Prader orchiometry
LH, FSH, testosterone
For postpubertal males:
Semen analysis
Reproductive endocrinology consultation for infertility
evaluation
SECOND MALIGNANT NEOPLASMS
CBC with differential
Doxorubicin, Etoposide
Cyclophosphamide
Urinalysis yearly
Pelvic radiotherapy
Neck radiotherapy
Thyroid palpation – imaging study if abnormal
Chest radiotherapy
Self breast-examination monthly
Mammogram annually to start 8 years following radiotherapy
or at age 25 years, whichever occurs last
Abdominal radiotherapy > 25 Gy
To start at 15 years post radiotherapy or at age 35 years,
whichever occurs last:
One of 3 options:
1.
Fecal occult blood (3 samples) yearly and flexible
sigmoidoscopy every 5 years OR
2.
Double contrast barium enema every 5 years OR
3.
Colonoscopy every 10 years
No specific risk factors
Follow American Cancer Society Recommendations
PSYCHOSOCIAL
Any therapy for cancer
Clinical interview yearly
Referral to mental health professional as clinically indicated
Abbreviations of screening tests: TSH: thyroid stimulating hormone; T4: thyroxine; LH: luteinizing hormone;
FSH: follicular stimulating hormone; CBC: complete blood count.
For those survivors, who have had an evaluation in the 6 months prior to study entry, with their consent, that
evaluation will be used for the study examination, or they may elect to wait an additional 6 m onths when
another clinical evaluation would be clinically indicated. Results from any screening m easures that were
collected previously, and not medically indicated to repeat during the study period, will be used for the study
purposes, with the consent of the participant. For ex ample, if a survivor is recom mended to have an
echocardiogram every 5 years, and one was done within a y ear of the study , it will not be repeated for study
purposes during the 4-year study period.
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For a m ore in-depth assessm ent of psy chosocial problems, participants also will com plete a self-report
psychologic assessment, which is em bedded in the study questionnaire, with questions regarding sleep,
fatigue, depression and symptoms of psychologic distress, quality of life, post traumatic growth and stress, and
sexual quality of life (See Data Forms on COG’s website).
4.2
Additional Data
Children’s Hospital and Regional Medical Center will be the coordinating institution for the study . All
data should be sent to Barbara Stansfeld (see contact information below).
4.3
Specimen Collection and Submission
The following data forms should be completed for each enrolled patient:
1.
Registration form
2.
Level of participation form
3.
Completed patient CCSS and psychosocial questionnaires
4.
Medical record abstraction form
5.
Clinical evaluation form
All forms should be sent to:
Barbara “Bobbi” Stansfeld
Clinical Research Associate (CRA III)
Seattle Children's Hospital
1900 Ninth Ave.
Mailstop C9S-9C
Seattle, WA 98101
Phone: (206) 884-1018
Fax: (206) 729-3062
4.4
Laboratory Analysis
Laboratory studies should be perform ed as indicated in the Late Effects Guidelines. Results should be
recorded on the clinical evaluation form.
5.0
STATISTICAL CONSIDERATIONS
5.1
Statistical Design
This is a cohort study with a comparison to historical controls.
5.2
Accrual (and Expected Duration of Accrual)
Contemporary subjects will be accrued from participating institutions and the study will be coordinated
by Children’s Hospital & Regional Medical Center in Seattle (CHRMC). Using the tumor registries and
divisional databases at the participating institutions , together with COG and PHC databases, we have
identified all eligible Hodgkin disease survivors, treat ed on or in parallel to the following protocols:
Children’s Cancer Group (CCG) 5942, 59704; Pediatric Oncology Group (POG) 8625, 8725, 9425, 9426;
Pediatric Hodgkin’s Consortium: VAMP, VEPA, VAMP/ COP, and the following institutional protocols:
COPP/ABV, MOPP/ABVD, ABVD.
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At the start of the first y ear, and throughout the study period, as needed, institutional principal investigators
will identify all currently eligible patients who are known lost to follow-up. They will submit demographic
data on those patients directly to the Tracking Resour ce Center (TRC) at Fred Hutchinson Cancer Research
Center (FHCRC), with whom they will contract in a business arrangem ent, for the purpose of tracking
patients. The TRC will procure current contact information for as many eligible patients as possible, using the
methodology described previously. The same methodology will be used for any eligible participants who are
found lost to follow-up during the research period. No demographic information that contains personal health
information will be released to the coordinating center at CHRMC until the participant has signed appropriate
informed consent. Institutions who require assistan ce with using the TRC should contact Barbara “Bobbi”
Stansfeld 206-884-1018 or [email protected].
We expect at least 1000 eligible HD patients in the cont emporary cohort and, with late relapse, loss to follow
up and refusals of as high as 20%, we will be able to study a minimum of 800 contemporary-cohort patients in
this study. Power calculations are therefore, conservatively based on 800 participants. However, given current
follow-up patterns and tracking, we will likely study more patients. In the earlier cohort treated in 1976-1986,
we have 1272 HD patients who participated in the CCSS. The total number of person-years among the 1272
patients during 5-15 years from the first cancer diagnosis was 10,275.79: we focus on the 5-15 y ears from the
diagnosis since this is the tim e period of observati on for the contem porary cohort. Our power calculations
below are tailored specifically to each of the three specific aims.
5.3
Statistical Analysis Methods
5.3.1 Data Analysis
Part 1: To characterize the incidence and spectrum of adverse physiological and psychological outcomes
in Hodgkin disease survivors treated with contemporary chemotherapy with or without involved field
radiotherapy, and compare with a cohort of patients treated from 1976 to 1986.
The first part will investigate each of adverse phy
siological conditions (i.e., cardiac toxicity , pulmonary
toxicity, thyroid dysfunction, gonadal dysfunction, and second malignant neoplasm as defined in Section D.3)
and psychological conditions (sy mptoms of depression or somatic distress, health-related quality of life,
sexual quality of life, fatigue, sleep, post traum atic stress, post traumatic growth) as separate outcom es. The
incidence rates of each condition will be com puted by the number of new occurrences, counting only the first
event of the adverse condition of interest, divided by the total number of person-years at risk. Each individual
will be considered to be at risk for a specific adver se condition until the earliest of death, developm ent of the
adverse condition, loss to follow up, or completion of questionnaire. The calculation of the incidence rates
will be done in two ways: (a) using the self-report incidence of adverse conditions; and (b) using the incidence
of adverse conditions validated by clinical evaluation.
Confidence intervals for the incidence rates will be calculated using the bootstrap m ethod via resampling
of survivors [106]. Cumulative incidence curves will also be produced to show the tim e of occurrence of
each condition after the entry to the study regarding mortality as the competing risk [107].
We will compare the incidence rates between survivors treated from 1987 to 2000 with those treated from
1976 to 1986. Note that this com parison will be based on self-report incidence of adverse conditions
since the earlier cohort will not have had uniform clinical evaluations. The ratio of the incidence rates for
the contemporary cohort over the earlier cohort will y ield a relative rate (RR) estim ate of each adverse
condition for the contemporary cohort. Specifically, we will use Cox proportional hazards modeling with
time from the 5 th-year survival to an occurrence of the event of interest as the failure time to be analyzed.
The regression will adjust for age at diagnosis, sex, and treated institutions in assessing the RR of m ain
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interest, i.e., the adjusted RR for the contem porary cohort com pared to the earlier cohort (1976-1986).
Since the set of study institutions differs between the earlier cohort and the contem porary cohort, we will
conduct a secondary sensitivity analysis by restricting the analysis to the institutions with both cohorts’
data and assessing the consistency in the contem porary-versus-earlier RR estim ate. Specifically , the
model will take the proportional hazard form:
(t) = o(t) exp (XT + ZT)
where (t) is the hazard of an adverse condition at time t from the 5-y ear survival of Hodgkin disease
(i.e., the entry to the CCSS study ), o denotes the baseline hazard, X is the indicator of contem porary
cohort membership, and Z is a vector of adjustm ent variables.  and  are parameters associated with X
and Z, respectively, of which our m ain focus will be on , the log hazard rate ratios of the adverse
condition of interest in the contem porary cohort relative to the earlier cohort, adjusting for Z. Standard
large-sample inference methods for a Cox regression parameter, , will be used to construct its confidence
limit and perform significance tests [108].
To investigate the factors that m odify the risk fo r the adverse conditions in the contem porary treatment
cohort, we will tabulate the incidence rates by various demographic and treatm ent categories. We will
explore variables such as sex, age, race/ethnicity, primary treatment modality, treatment with alkylating
agents, treatment with doxorubicin, treatment with bleomycin, and treatment with radiotherapy, and doses
of these therapies. For the exploratory tabulation, we will use Poisson regression models to summarize the
rates and their modification by the significant demographic and treatment characteristics, simultaneously.
Specifically, the model takes the following log-linear form with an offset term:
log E[Yij] = log PYij + XijT,
Yij’s are independent Poisson random variables with means E[Yi]’s,
where Yij, PYij, and Xij are the indicator of an adverse condition occurrence, person-tim e at risk, and a
vector of dem ographic/treatment factors, respectively, in ith survivor’s j th time segment, and  is the
parameter vector of interest, log relative rates associated with covariates
X. Note that the piece-wise
constant hazards for time segments permit the use of time-dependent covariates in this analysis. Standard
large-sample inference methods for generalized linear m odels will be used to construct interval estim ates
and perform significance tests for  [109].
Part 2: To validate self-reported health-related outcom es of Hodgkin disease survivors, including both new
cohort and CCSS cohort, with clinical evaluation.
For the CCSS cohort (the earlier cohort), we will obtai n medical records to validate 700 positive responses for
targeted conditions reported between 5 and 15 years from diagnosis. For the contemporary cohort, we will use
a combination of medical records and clinical eval uations to validate all sel f-reported positive and negative
responses for targeted conditions. For purposes of assessing validity, medical records and clinical evaluation
will be used as the 'gold standard'. If a condition is mentioned in the medical record or clinical evaluation, it is
assigned a ' yes' value, otherwise it is assigned a '
no' value. Similarly, each response in the self-report
questionnaire is recorded as a 'yes' value for a positive r esponse and a 'no' value for a negative response in the
corresponding categories.
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Sensitivity and specificity validity measures of the qu estionnaire will be calculated for binom ial categorical
variables. The term 'sensitivity' is defined as the propor tion of those with the com plication (as defined by the
medical records/clinical evaluations) who are correctly classified by the questionnaire. ' Specificity' is the
proportion of the study population that truly does not have the complication and is correctly reported in the
questionnaire. We will also obtain validation statisti cs such as positive predictive value (PPV) of self report,
defined as the proportion of true positives among those reported as positives in the questionnaire, and negative
predictive value (NPV), defined as proportion of tr ue negatives among those reported as negatives in the
questionnaire. For the earlier cohort (1976-1986), our medical-record-based validation will be limited to those
who self reported adverse events (i.e., negative self reports will not be validated). For this reason, we will
calculate PPV only for the earlier cohort. Our statisti cal inference regarding sensitivity, specificity, PPV, and
NPV will be based on the standard binomial-based methods for evaluating medical diagnostic tests discussed
by Pepe [110].
5.3.2 Power calculations:
Aim 1. Descriptive incidence rates
In the contemporary cohort of 800 survivors, we expect approximately 6,000 person-years based on the total
person-years observed in the earlier cohort in the peri od of 5-15 y ears from the first cancer diagnosis. The
precision of a descriptive rate can be represented by its expected width of confidence intervals. Under the
standard Poisson assumption of event occurrences, the e xpected width of a 95% confidence interval for the
incidence rate per 10,000 person-years will be 1.96()0.5 x 10/6, where 10/6 is the underlying incidence rate
per 10,000 person-y ears. Thus, the expected widths (i.e., the precision of
our incidence estimates) are as
follows:
Incidence rates per
10,000 person-years
Precision (CI width)
50
100
150 200 250 300 350
400
450 500
17.9 25.3 31.0 35.8 40.0 43.8 47.3 50.6 53.7 56.6
Aim 2. Earlier vs. contemporary comparison
This will be a com parison of two independent groups with respect to adverse condition incidence using
Cox regression. The reference group is the earlie r cohort of 1272 HD survivors with approxim ately
10,000 person-years of follow-up and the com parison group is the contemporary cohort of 800 survivors
with approximately 6,000 person-y ears of follow-up. Our calculation of power for this com parison is
based on the method proposed by Lachin and Foulkes for failure-time data analysis. With the type I error
probability of 0.05 and a two-sided test, we will have the following power [111]:
Cumulative incidence of an adverse
condition in the earlier cohort
5%
10%
 15%
Rate ratio (contemporary vs. earlier)
0.5
0.3
62%
94%
91%
>99%
>96%
>99%
Thus, if the cumulative incidence of an adverse condition in the earlier cohort is greater than 10%, we will
have sufficient power to detect a rate ratio of 0. 5 or smaller comparing the contemporary cohort to the
earlier cohort. If the cumulative incidence of an adverse condition in the earlier cohort is 5%, we will not
have sufficient power to detect a rate ratio of 0.5 but have sufficient power to detect a rate ratio of 0.3 or
smaller.
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Aim 3. Validity of self-report against medical record/clinical evaluation
With 800 survivors and a cum ulative incidence of 100%, we will have 800 true positives and 800(1-)
true negatives. T he precision of sensitivity estimate, approximated by the width of a 95% confidence
interval, will be 1.96{p(1-p)}0.5/(800), where p is the true sensitivity . Sim ilarly, the precision of
specificity estimate will be 1.96{p*(1-p*)}0.5/{800(1-)}, where p* is the true specificity . Thus, the
precision of our sensitivity/specificity estimates will be as follows:
Cumulative incidence of
an adverse condition
5%
10%
30%
50%
Sensitivity / Specificity
70%
2.2% / 0.1%
1.1% / 0.1%
0.4% / 0.2%
0.2% / 0.2%
80%
2.0% / 0.1%
1.0% / 0.1%
0.3% / 0.1%
0.2% / 0.2%
90%
1.5% / 0.1%
0.7% / 0.1%
0.2% / 0.1%
0.1% / 0.1%
95%
1.1% / 0.1%
0.5% / 0.1%
0.2% / 0.1%
0.1% / 0.1%
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This model informed consent form has been reviewed by the DCT/NCI and is the official
consent document for this study. Institutions should use the sections of this document which are
in bold type in their entirety. Editorial changes to these sections may be made as long as they
do not change information or intent. If the local IRB insists on making deletions or more
substantive modifications to any of the sections in bold type, they must be justified in writing by
the investigator at the time of the institutional audit.
SAMPLE INFORMED CONSENT
ALTE04N1: Health-Related Outcomes for Hodgkin Survivors
If you are a parent or legal guardian of a child who may take part in this study, permission from
you is required. The assent (agreement) of your child may also be required. When we say “you”
in this consent form, we mean you or your child; “we” means the doctors and other staff.
WHAT IS THIS STUDY ABOUT?
This study is a clinical trial (a research study involving human patients). Clinical trials only
include patients who choose to take part. Please take your time to make your decision. You may
want to discuss your decision with your friends and family.
This study is being carried out by the Children’s Oncology Group (COG). The COG is an
international research group that consists of more than 200 hospitals that treat children with
cancer in the United States, Canada, Australia, New Zealand, the Netherlands and Switzerland.
Much is known about the late effects of treatment for Hodgkin Disease diagnosed before 1987. As
a result of that knowledge, treatment was changed in the late 1980’s to decrease those effects. This
study is an attempt to find out how survivors are doing after receiving these newer treatments in
order to try and help patients treated for Hodgkin Disease after 1987 and future children who are
diagnosed with Hodgkin Disease.
You/your child are invited to participate in this research study because you/your child was
diagnosed and treated for Hodgkin Disease at Children’s Hospital and Regional Medical Center.
You/your child were/was treated on a Children’s Oncology Group, Children’s Cancer Group,
Pediatric Oncology group or similar protocol between 1987 and 2000.
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to learn how survivors are doing after receiving these newer
treatments. The possible late effects of treatment that we will be looking for with this
research study are:
 Heart problems.
 Lung problems.
 Endocrine (hormone) problems.
 Gonadal problems (problems having children).
 Second cancers.
 Psychological and social problems relating to health-related quality of life, sexual
quality of life, fatigue, post-traumatic stress, post traumatic growth*, and depression.
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* Post traumatic growth is the opposite of post traumatic stress. It refers to survivors, who after
going through the "trauma" of cancer and its therapy, grow psychologically from the experience.
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?
About 800 people will take part in this study.
WHAT WILL HAPPEN TO ME ON THIS STUDY?
If you/your child decide to take part in this research study you/your child will complete a
questionnaire about your/your child’s current health, family medical history, and health behaviors.
This will take 45 – 90 minutes to complete. This questionnaire can be completed by you/your child
in written format or it can be administered by telephone interview, whichever is more convenient for
you. You/your child will also be scheduled for a comprehensive risk-based evaluation. This
evaluation will include examinations and testing recommended by the Children’s Oncology Late
Effects Screening Guidelines.
o
Complete health history and review of systems.
o
Complete physical examination.
o
Laboratory tests: blood and urine evaluation.
o
Diagnostic imaging studies: tests to look at the function of your/your child’s heart,
lungs, and hormones. There may also be cancer screenings, such as
mammograms for women (to start 8 years after radiotherapy or by 25 years,
whichever occurs last) and tests to look at your/your child’s stomach and colon (to
start at 15 years post radiotherapy or at age 35, whichever happens last).
o
Age and gender (male or female) specific pubertal and reproductive evaluations.
For girls older than 11, they may have their hormones tested if they failed to go
through puberty. For girls who already went through puberty, they will be offered a
chance to meet with an infertility specialist if they were unable to get pregnant
and/or have irregular menstrual cycles. For boys older than 11, they may have
their hormones evaluated. For boys who already have already gone through
puberty, they will be offered a chance to have their sperm evaluated and they
and/or their parents may meet with an infertility specialist if they are interested in
having children.
o
Psychological evaluation.
You will receive a written summary of your evaluation with recommendation for future care and
observation. In addition, we will be reviewing your/your child’s medical record. We will be collecting
information about past health problems that may have resulted from treatment for Hodgkin Disease.
We will collect information on the results of routine tests done to check for late effects, such as
blood tests, tests of heart function. We are only using results that are in your/your child’s medical
record. We will ask you/your child to sign a Release of Information Form to obtain records from
your/your child’s primary medical doctor. We will only gather information from your/your child’s
primary medical doctor that may be related to late effects of treatment for Hodgkin Disease.
HOW LONG WILL I (MY CHILD) BE IN THE STUDY?
You will be on this study for as long as it takes to complete the questionnaires,
usually 45-60 minutes. (The clinical evaluation tests are part of routine follow up and
should not require an additional visit to your/your child’s treating institution).
We would like to keep track of your medical condition for at least five years. Keeping in touch
with you and checking on your condition every year helps us look at the long-term effects of the
study.
WHAT ARE THE RISKS OF THE STUDY?
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Some of the questions in the questionnaires are of a personal nature and may make
you/your child feel uncomfortable. For example, questions will be asked about smoking,
alcohol use, and ability to have children. We will also be asking questions about
your/your child’s emotions and feelings. The questionnaires that are being used for this
research study have been used many times by many hospitals and clinics. To the best of
our knowledge they have not caused anyone serious problems. You/your child do not
have to answer any question that you/your child don’t want to. Simply leave the answer
blank on the questionnaire.
The participant/family may experience distress as they learn about potential health risks
of treatment of which they were not previously aware. If a participant/family experiences
distress, we can make a referral to an experienced social worker to help resolve distress
or discomfort.
All of the blood work is standard of care so there is no added risk from a blood draw since you/your
child will already having blood drawn for routine follow up.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
Each participant will receive a comprehensive risk-based evaluation, along with appropriate health
education. This may result in an improved quality of life and improved future health.
We hope that the information gained from this research study will help other patients with Hodgkin
Disease in the future.
WHAT OTHER OPTIONS ARE THERE?
You have (your child has) the option of choosing not (to have your child) participate in
this study.
You may want to discuss this option with your (child’s) regular doctor as well as other
trusted personal and family advisors.
WHAT ABOUT CONFIDENTIALITY?
Efforts will be made to keep your personal information confidential. We cannot guarantee
absolute confidentiality. Your personal information may be disclosed if required by law.
The Children’s Oncology Group has received a Certificate of Confidentiality from the federal
government, which will help us protect the privacy of our research subjects. Information about
the certificate is included in Attachment #1.
Organizations that may inspect/or copy your (child’s) research records for quality
assurance and data analysis include:
 The Children’s Oncology Group (COG);
 The National Cancer Institute (NCI);
 The Food and Drug Administration (FDA);
 The Institutional Review Board of this hospital (IRB); and
 Children’s Hospital and Regional Medical Center, University of Washington
WHAT ARE THE COSTS?
The evaluations recommended as part of this study are considered standard of care for longterm survivors of Hodgkin disease. You and/or your health plan/ insurance company will need
to pay for some or all of the evaluation costs. Some health plans will not pay these costs for
people taking part in studies. Check with your health plan or insurance company to find out
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what they will pay for. Taking part in this study may or may not cost your insurance company
more than the cost of getting regular cancer treatment. If you/your insurance cannot pay for the
recommended evaluations, please discuss this with your physician.
You will not be paid for taking part in this study
For more information on clinical trials and insurance coverage, you can visit the National Cancer
Institute's Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage . You can
print a copy of the "Clinical Trials and Insurance Coverage" information from this Web site.
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them to
send you a free copy.
WHAT ARE MY (AND MY CHILD’S) RIGHTS AS A PARTICIPANT?
Taking part in this study is voluntary. You may choose (for your child) not to participate in this
study. If you decide not to (let your child) participate, you (your child) will not be penalized and
you (your child) will still receive treatment as agreed upon with your (child’s) primary doctor.
If you choose to (allow your child to) participate, you may discontinue your (child’s) participation
in the study at any time. If you discontinue participation in the study, physicians and hospital
personnel will still take care of you (your child). Whether you participate or not, you (your child)
will continue to get the best medical care this hospital can provide.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or if you have a research related problem or if you think you have
been injured, contact Dr. XXXX or your doctor at XXXXX
If you have any questions about your rights as a research participant or any problems that you
feel you cannot discuss with the investigators, you may call XXXX IRB Administrator at (XXXX
If you have any questions or concerns that you feel you would like to discuss with someone who
is not on the research team, you may also call the Patient Advocate at XXXX
WHERE CAN I GET MORE INFORMATION?
The COG Family Handbook for Children with Cancer has information about specific cancers,
tests, treatment side effects and their management, adjusting to cancer, and resources. Your
doctor can get you this Handbook, or you can get it at www.curesearch.org/
Visit the NCI's Web site at http://www.nci.nih.gov/cancerinfo/
If you are in the United States, you may call the NCI's Cancer Information Service at:
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615
Information about long term follow-up
http://www.survivorshipguidelines.org/
after
cancer
treatment
can
be
found
at:
You will get a copy of this form. You may also ask for a copy of the protocol (full study plan).
SIGNATURE
Page 31
ALTE04N1
I have been given a copy of all _____ pages of this form. The form includes one (1)
attachment.
I have reviewed the information and have had my questions answered.
I agree to take part in this study.
Participant
Date
Parent/Guardian
Date
Parent/Guardian
Date
Physician/PNP obtaining consent
Date
IRB#
Page 32
ALTE04N1
Attachment #1
Certificate of Confidentiality
The Children's Oncology Group has received a Certificate of Confidentiality from the federal
government, which will help us protect the privacy of our research subjects. The Certificate protects
against the involuntary release of information about subjects collected during the course of our
covered studies. The researchers involved in the studies cannot be forced to disclose the identity
or any information collected in the study in any legal proceedings at the federal, state, or local level,
regardless of whether they are criminal, administrative, or legislative proceedings. However, the
subject or the researcher may choose to voluntarily disclose the protected information under certain
circumstances. For example, if the subject or his/her guardian requests the release of information
in writing, the Certificate does not protect against that voluntary disclosure. Furthermore, federal
agencies may review our records under limited circumstances, such as a DHHS request for
information for an audit or program evaluation or an FDA request under the Food, Drug and
Cosmetics Act.
The Certificate of Confidentiality will not protect against the required reporting by hospital staff of
information on suspected child abuse, reportable communicable diseases, and/or possible threat of
harm to self or others.
Page 33

ALTE04N1 Activated: 10/18/2004 Version Date:

Transcription

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