S9901 Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Men With Stage III or Stage IV Hodgkin's Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Lymphoma	Biological: bleomycin sulfate Drug: carmustine Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide Drug: vinblastine Procedure: peripheral blood stem cell transplantation	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hodgkin Disease Lymphoma

Drug Information available for: Cyclophosphamide Vinblastine sulfate Carmustine Vinblastine Dacarbazine Bleomycin sulfate Bleomycin Doxorubicin Doxorubicin hydrochloride Etoposide Etoposide phosphate

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Progression-free survival [ Time Frame: every 3 months while on protocol treatment, then every 6 months for 2 years, then annually thereafter ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

overall survival [ Time Frame: every 3 months while on treatment, then every 6 months thereafter ] [ Designated as safety issue: No ]

Enrollment:	11
Study Start Date:	April 2000
Study Completion Date:	May 2005
Primary Completion Date:	May 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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.	Biological: bleomycin 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. Drug: dacarbazine 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. Drug: doxorubicin 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. Drug: vinblastine 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.
Experimental: 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.	Biological: bleomycin 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. Drug: carmustine 150/m^2 on days -6 to -4 (4-6 days before transplant). Other Name: BCNU Drug: cyclophosphamide 100 mg/kg on day -2 (2 days before transplant). Drug: dacarbazine 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. Drug: doxorubicin 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. Drug: etoposide 60 mg/kg on day -4 (4 days before transplant). Drug: vinblastine 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. Procedure: peripheral blood stem cell transplantation 2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight

Arms

Assigned Interventions

Active Comparator: 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.

Biological: bleomycin 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.

Drug: dacarbazine

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.

Drug: doxorubicin 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.

Drug: vinblastine

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.

Experimental: 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.

Biological: bleomycin 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.

Drug: carmustine

150/m^2 on days -6 to -4 (4-6 days before transplant).

Other Name: BCNU

Drug: cyclophosphamide

100 mg/kg on day -2 (2 days before transplant).

Drug: dacarbazine

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.

Drug: doxorubicin 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.

Drug: etoposide

60 mg/kg on day -4 (4 days before transplant).

Drug: vinblastine

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.

Procedure: peripheral blood stem cell transplantation

2 x 10^6 CD34+ blood mononuclear cells/kg of actual body weight

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.

Eligibility

Ages Eligible for Study:	15 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005090

Show 47 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Cancer and Leukemia Group B

Investigators

Study Chair:	Ellen R. Gaynor, MD	Loyola University
Study Chair:	Sandra J. Horning, MD	Stanford University
Study Chair:	Linda J. Burns, MD	Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00005090 History of Changes
Other Study ID Numbers:	CDR0000067708, S9901, CLB-59802, E-S9901, U10CA032102
Study First Received:	April 6, 2000
Last Updated:	January 22, 2013
Health Authority:	United States: Federal Government

Keywords provided by Southwest Oncology Group:

stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Etoposide phosphate
Carmustine
Cyclophosphamide
Dacarbazine
Etoposide

Vinblastine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators

ClinicalTrials.gov processed this record on June 17, 2013