A Randomized Phase III Trial Comparing Early High Dose Chemotherapy and an Autologous Stem Cell Transplant to Conventional Dose ABVD Chemotherapy for Patients With Advanced Stage Poor Prognosis Hodgkin's Disease as Defined by the International Prognostic Factors Project on Advanced Hodgkin's Disease
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- SWOG Cancer Research Network
- Enrollment
- 11
- Locations
- 47
- Primary Endpoint
- Progression-free survival
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 15 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
ABVD x 5 + ABVD x 3
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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.
Intervention: bleomycin sulfate (Biological)
ABVD x 5 + ABVD x 3
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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.
Intervention: dacarbazine (Drug)
ABVD x 5 + ABVD x 3
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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.
Intervention: doxorubicin hydrochloride (Drug)
ABVD x 5 + ABVD x 3
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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.
Intervention: vinblastine (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: bleomycin sulfate (Biological)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: carmustine (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: cyclophosphamide (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: dacarbazine (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: doxorubicin hydrochloride (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: etoposide (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: vinblastine (Drug)
ABVD x 5 + ABVD x 1 + HDT + PBSCT
Patients receive 5 28-day cycles of ABVD (doxorubicin 25 mg/m^2, bleomycin 10 U/m^2, vinblastine 6 mg/m^2, dacarbazine 375 mg/m^2 all on days 1 and 15). 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. Patients randomized to the transplant arm have 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight collected at day -7. High dose therapy consists of BCNU 150/m^2 on days -6 to -4, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Peripheral blood stem cells are infused on day 0.
Intervention: peripheral blood stem cell transplantation (Procedure)
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: every 3 months while on protocol treatment, then every 6 months for 2 years, then annually thereafter
Secondary Outcomes
- overall survival(every 3 months while on treatment, then every 6 months thereafter)