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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005090
• Other study ID #: CDR0000067708
• Secondary ID: S9901CLB-59802E-
• Status: Terminated
• Phase: Phase 3
• First received: April 6, 2000
• Last updated: January 22, 2013
• Start date: April 2000
• Est. completion date: May 2005

Study information

• Verified date: January 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

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).
• cyclophosphamide
100 mg/kg on day -2 (2 days before transplant).
• 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.
• 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.
• etoposide
60 mg/kg on day -4 (4 days before transplant).
• 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

Locations

Country	Name	City	State
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	University of California San Diego Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Schneider Children's Hospital at North Shore	Manhasset	New York
United States	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee
United States	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Rhode Island Hospital	Providence	Rhode Island
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	Veterans Affairs Medical Center - Togus	Togus	Maine
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Southwest Oncology Group	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		every 3 months while on protocol treatment, then every 6 months for 2 years, then annually thereafter	No
Secondary	overall survival		every 3 months while on treatment, then every 6 months thereafter	No