Clinical trial NCT00003389
Conditions: Lymphoma
Keywords: stage I adult Hodgkin lymphoma stage II adult Hodgkin lymphoma stage III adult Hodgkin lymphoma stage IV adult Hodgkin lymphoma adult lymphocyte depletion Hodgkin lymphoma adult nodular sclerosis Hodgkin lymphoma adult mixed cellularity Hodgkin lymphoma
Sponsor: Eastern Cooperative Oncology Group
Start date: 1999-06-17; Completion date: 2016-05-01
Enrollment: 854 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining more than one drug with radiation therapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is most effective in treating Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work, with or without radiation therapy, in treating patients with Hodgkin's lymphoma.

Detailed description:
OBJECTIVES:

* 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.
* Compare the overall survival and freedom from progression in these patients at 5 and 10 years after treatment with these regimens.
* Compare pulmonary function, incidence of second cancers, reproductive function, and deaths from causes other than Hodgkin's lymphoma in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to number of adverse risk factors (0-2 vs 3-7), disease characteristics (locally extensive vs advanced) and time of entry (before addendum 6 vs. after addendum 6). Patients are randomized to 1 of 2 treatment arms.

* Arm A (ABVD): Patients receive doxorubicin (25 mg/m²), bleomycin (10 u/m²), vinblastine (6 mg/m²), and dacarbazine (375 mg/m²) 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 B (Stanford V): Patients receive Stanford V chemotherapy comprising doxorubicin (25 mg/m²) and vinblastine (6 mg/m²) IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine (1.4 mg/m²) and bleomycin (5 u/m²) IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine (6 mg/m²) IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide \[375 mg/m²\] IV); etoposide (60 mg/m²) IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone (40 mg/m²) 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.

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

Arms: arm 1: Arm A (ABVD): Patients receive doxorubicin (25 mg/m²), bleomycin (10 u/m²), vinblastine (6 mg/m²), and dacarbazine (375 mg/m²) intravenously (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 2: Arm B (Stanford V): Patients receive Stanford V chemotherapy comprising doxorubicin (25 mg/m²) and vinblastine (6 mg/m²) IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine (1.4 mg/m²) and bleomycin (5 u/m²) IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine (6 mg/m²) IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide \[375 mg/m²\] IV); etoposide (60 mg/m²) IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone (40 mg/m²) 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.
Interventions: intervention 1: Doxorubicin intervention 2: Bleomycin intervention 3: Vinblastine intervention 4: Dacarbazine intervention 5: Vincristine intervention 6: Mechlorethamine intervention 7: Etoposide intervention 8: Prednisone intervention 9: Cyclophosphamide intervention 10: Radiotherapy
Intervention descriptions: intervention 1: given IV intervention 2: given IV intervention 3: given IV intervention 4: given IV intervention 5: given IV intervention 6: given IV intervention 7: given IV intervention 8: taken orally intervention 9: given IV intervention 10: None

Protocol documents: