Lymphoma
Conditions
Keywords
stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without peripheral stem cell transplantation in treating Hodgkin's Disease. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without peripheral stem cell transplantation in treating men who have stage III or stage IV Hodgkin's disease.
Detailed description
OBJECTIVES: * Compare progression-free and overall survival of patients with stage III or IV Hodgkin's disease treated with doxorubicin, bleomycin, vinblastine, and dacarbazine with or without autologous peripheral blood stem cell transplantation and high-dose chemotherapy. * Compare the toxic effects of these treatment regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of poor prognostic factors (3 vs 4 vs 5) and stage of disease (III vs IV). Patients receive induction chemotherapy consisting of doxorubicin IV over 5 minutes, bleomycin IV over 10 minutes, vinblastine IV over 5 minutes, and dacarbazine IV over 15-30 minutes on days 1 and 15. Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients who show at least partial response after the fifth course of induction chemotherapy and whose blood counts have recovered are randomized to 1 of 2 treatment arms. * Arm I: Patients receive 3 additional courses of induction chemotherapy for a total of 8 courses. * Arm II: Patients receive 1 additional course of induction chemotherapy followed by stem cell collection. Patients then receive high-dose chemotherapy with carmustine IV over 2 hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2. Patients undergo autologous peripheral blood stem cell transplantation on day 0. Patients are followed at 60 days, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 460 patients will be accrued for this study within 4 years.
Interventions
BIOLOGICALbleomycin sulfate
10 U/m\^2 given on days 1 and 15 for 5 28-day cycles of ABVD. Patients with no disease progression are then randomized to either 3 more cycles of ABVD or 1 more cycle of ABVD + high-dose therapy + stem cell transplant.
DRUGcarmustine
150/m\^2 on days -6 to -4 (4-6 days before transplant).
DRUGcyclophosphamide
100 mg/kg on day -2 (2 days before transplant).
DRUGdacarbazine
375 mg/m\^2 on days 1 and 15 for 5 28-day cycles of ABVD. Patients with no disease progression are then randomized to either 3 more cycles of ABVD or 1 more cycle of ABVD + high-dose therapy + stem cell transplant.
DRUGdoxorubicin hydrochloride
25 mg/m\^2 on days 1 and 15 for 5 28-day cycles of ABVD. Patients with no disease progression are then randomized to either 3 more cycles of ABVD or 1 more cycle of ABVD + high-dose therapy + stem cell transplant.
DRUGetoposide
60 mg/kg on day -4 (4 days before transplant).
DRUGvinblastine
6 mg/m\^2 on days 1 and 15 for 5 28-day cycles of ABVD. Patients with no disease progression are then randomized to either 3 more cycles of ABVD or 1 more cycle of ABVD + high-dose therapy + stem cell transplant.
PROCEDUREperipheral blood stem cell transplantation
2 x 10\^6 CD34+ blood mononuclear cells/kg of actual body weight
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed stage III or IV Hodgkin's disease with at least 3 of the following characteristics: * Albumin less than 4.0 mg/dL * Hemoglobin less than 10.5 g/dL * Leukocytosis at least 15,000/mm\^3 * Lymphocytopenia less than 600/mm\^3 or less than 8% of total WBC * Male sex * At least 45 years of age * Stage IV disease * Bidimensionally measurable disease * Bilateral or unilateral bone marrow aspiration and biopsy performed within 42 days of study * Negative chest x-ray within 42 days of study OR * Chest x-ray performed within 28 days of study * Negative CT scan of thorax, abdomen, and pelvis within 42 days of study OR * CT scan of thorax, abdomen, and pelvis performed within 28 days of study * No history of lymphoma, myelodyplastic syndrome, or leukemia * No CNS involvement by Hodgkin's disease PATIENT CHARACTERISTICS: Age: * 15 to 65 Performance status: * Zubrod 0-1 Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * See Disease Characteristics * Bilirubin no greater than 1.5 times upper limit of normal (ULN) (unless elevation due to liver infiltration by Hodgkin's disease) * Lymphoma-related hepatic dysfunction allowed Renal: * Creatinine no greater than 2.0 times ULN * Creatinine clearance at least 60 mL/min * Lymphoma-related renal dysfunction allowed Cardiovascular: * No coronary artery disease, cardiomyopathy, congestive heart failure, or arrhythmias requiring therapy * Ejection fraction normal * No significant EKG abnormalities suggesting active cardiac disease Pulmonary: * Corrected DLCO at least 60% OR * FEV1 at least 60% predicted Other: * Not pregnant or nursing * Fertile patients must use effective contraception * No HIV or AIDS * No other prior malignancy within past 5 years except adequately treated basal cell or squamous cell skin cancer * No active bacterial, fungal, or viral infection\* * Afebrile for 3 consecutive days\* NOTE: \*Prior to randomization portion of study PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior chemotherapy for Hodgkin's disease except single course of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) within 35 days of study Endocrine therapy: * Not specified Radiotherapy: * No prior radiotherapy for Hodgkin's disease Surgery: * Not specified Other: * At least 3 days since prior antibiotics, antifungals, or antivirals (except for prophylactic therapy or fever associated with underlying lymphoma) (for randomization portion of study)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival | every 3 months while on protocol treatment, then every 6 months for 2 years, then annually thereafter |
Secondary
| Measure | Time frame |
|---|---|
| overall survival | every 3 months while on treatment, then every 6 months thereafter |
Countries
United States
Outcome results
None listed