Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	16 and over	NCI	ECOG-2496 CAN-NCIC-HD7, CALGB-59905, SWOG-E2496, E2496, NCT00003389, HD7

Objectives

1. Compare the failure-free survival of patients with locally extensive or advanced Hodgkin's lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) vs doxorubicin, vinblastine, vincristine, bleomycin, mechlorethamine, etoposide, and prednisone (Stanford V) with or without radiotherapy.
2. Compare the overall survival and freedom from progression in these patients at 5 and 10 years after treatment with these regimens.
3. Compare pulmonary function, incidence of second cancers, reproductive function, and deaths from causes other than Hodgkin's lymphoma in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically proven previously untreated classical Hodgkin's lymphoma of the following subtypes:
  • Nodular sclerosis
  • Mixed cellularity
  • Lymphocyte depletion
  • Lymphocyte rich



• The following stages are eligible:
  • Stage I-IIA/B with massive mediastinal adenopathy
  • Stage III or IV



• Measurable or evaluable disease

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• Prior surgery allowed

Patient Characteristics:

Age:

• 16 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm³ (unless documented bone marrow involvement)
• Platelet count at least 100,000/mm³ (unless documented bone marrow involvement)

Hepatic:

• Bilirubin no greater than 5.0 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Ejection fraction determination recommended if over age 50 and/or have a history of cardiac disease

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

A total of 850 patients will be accrued for this study within 4.3 years.

Outcomes

Failure-free survival as measured by two-sided 0.05 level logrank test at completion of therapy and then every 6 months for 3 years
Overall progression-free survival by two-sided 0.05 level logrank test 5 and 10 years following study completion

Pulmonary function by forced vital capacity and DLCO at baseline and 5 years following study completion
Second cancers
Reproductive function by Reproductive Health Assessment questionnaire, semen analysis, follicle-stimulating hormone, and luteinizing hormone at baseline and 5 years following study completion
Deaths from causes other than Hodgkin's disease
Corr. new EBV detect. tech. in plasma and tumor tissue w/ cytotoxic T-cell response to EBV antigens and antigens from other viruses before study tx, at 1 wk, at 1 mo. after compl. of tx, & 1 year from study entry
Corr. new EBV detect. tech. in plasma and tumor tiss. w/ impact of chemotherapy and/or radiotherapy on T-cell responses to EBV ags and ags from other viruses before study tx, at 1 wk, at 1 mo. after compl. of tx, & 1 year from study entry

Outline

This is a randomized study. Patients are stratified according to number of adverse risk factors (0-2 vs 3-7) and disease characteristics (locally extensive vs advanced). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive doxorubicin, bleomycin, vinblastine, and dacarbazine IV on days 1 and 15. Courses repeat every 28 days. Patients are restaged after 4 courses. Patients who are in complete remission receive 2 additional courses. Patients with a partial response or less are evaluated after 6 courses, and if there is an ongoing response, patients may receive 2 additional courses for a total of 8. If no ongoing response is observed, patients are removed from the study. All patients with massive mediastinal disease, regardless of stage, receive radiotherapy 2-3 weeks after completion of chemotherapy.



• Arm II: Patients receive Stanford V chemotherapy comprising doxorubicin and vinblastine IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine and bleomycin IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide IV); etoposide IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone every other day of weeks 1-9 followed by a taper. All patients with bulky disease receive radiotherapy 2-3 weeks after completion of chemotherapy.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Sandra Horning, MD, Protocol chair		Ph: 650-725-6456; 800-756-9000

Southwest Oncology Group

Richard Fisher, MD, Protocol chair		Ph: 585-275-0842 Email: richard_fisher@urmc.rochester.edu

NCIC-Clinical Trials Group

Joseph Connors, MD, Protocol chair		Ph: 604-877-6000 ext. 2746; 800-663-3333 Email: jconnors@bccancer.bc.ca

Cancer and Leukemia Group B

Nancy Bartlett, MD, Protocol chair		Ph: 314-362-5654; 800-600-3606

Registry Information
Official Title		A Randomized Phase III Trial of ABVD Versus Stanford V(+/-) Radiation Therapy in Locally Extensive and Advanced Stage Hodgkin's Disease Without High Risk Features
Trial Start Date		2000-11-06
Registered in ClinicalTrials.gov		NCT00003389
Date Submitted to PDQ		1998-06-24
Information Last Verified		2006-07-03
NCI Grant/Contract Number		CA21115