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

NCT ID: NCT00005090

Last Updated: 2013-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-04-30

Study Completion Date

2005-05-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

bleomycin sulfate

Intervention Type BIOLOGICAL

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.

dacarbazine

Intervention Type DRUG

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.

doxorubicin hydrochloride

Intervention Type DRUG

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.

vinblastine

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

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.

carmustine

Intervention Type DRUG

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

cyclophosphamide

Intervention Type DRUG

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

dacarbazine

Intervention Type DRUG

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.

doxorubicin hydrochloride

Intervention Type DRUG

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.

etoposide

Intervention Type DRUG

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

vinblastine

Intervention Type DRUG

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.

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

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

Interventions

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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.

Intervention Type BIOLOGICAL

carmustine

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

Intervention Type DRUG

cyclophosphamide

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

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

etoposide

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

Intervention Type 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.

Intervention Type DRUG

peripheral blood stem cell transplantation

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

Intervention Type PROCEDURE

Other Intervention Names

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BCNU

Eligibility Criteria

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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)
Minimum Eligible Age

15 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ellen R. Gaynor, MD

Role: STUDY_CHAIR

Loyola University

Sandra J. Horning, MD

Role: STUDY_CHAIR

Stanford University

Linda J. Burns, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

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Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, United States

Site Status

Veterans Affairs Medical Center - Togus

Togus, Maine, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Schneider Children's Hospital at North Shore

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

Green Mountain Oncology Group

Bennington, Vermont, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Site Status

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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S9901

Identifier Type: OTHER

Identifier Source: secondary_id

CLB-59802

Identifier Type: OTHER

Identifier Source: secondary_id

E-S9901

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067708

Identifier Type: -

Identifier Source: org_study_id

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