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Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed or Progressive B-Cell Diffuse Large Cell Lymphoma

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00052923
First received: January 24, 2003
Last updated: February 6, 2009
Last verified: June 2006
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether stem cell transplantation is more effective with or without rituximab in treating relapsed or progressive B-cell diffuse large cell lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of stem cell transplantation with or without rituximab in treating patients who have relapsed or progressive B-cell diffuse large cell lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial Of Rituximab (NSC #687451) And Autologous Stem Cell Transplantation For B Cell Diffuse Large Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Procedure-related mortality [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Potential infectious complications of the addition of rituximab to autologous stem cell transplantation [ Designated as safety issue: No ]

Estimated Enrollment: 427
Study Start Date: March 2003
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare disease-free survival of patients with relapsed or progressive B-cell diffuse large cell lymphoma undergoing stem cell transplantation with or without post-transplant rituximab.
  • Evaluate the effect of rituximab, administered post-transplant, on the procedure-related mortality of these patients.
  • Determine the potential infectious complications of the addition of this drug to autologous stem cell transplantation in these patients.
  • Compare overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to relapse (relapsed more than 6 months after either initial complete remission [CR] or CR with positive positron emission tomography or MRI [gallium] vs failed to achieve initial CR or relapsed within 6 months after either initial CR or CR with positive PET or MRI [gallium]) and prior rituximab (yes vs no).

Stem cell mobilization

  • Patients receive rituximab IV over 4-8 hours on days 1 and 5. Patients also receive cyclophosphamide IV over 2 hours on day 8 and filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until the last day of apheresis. Stem cells are collected over 1-3 days.

Preparative regimen

  • Regimen A (patients who have received prior radiotherapy or are ≥ 61 years of age): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2.
  • Regimen B (all other patients): Patients undergo total body irradiation twice daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2.

Stem cells are reinfused on day 0. Patients are then randomized to one of two post-transplant treatment arms.

Post-transplant treatment

  • Arm I (rituximab): Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Patients receive rituximab IV over 4-8 hours every 7 days for 4 doses, starting on day 45 post-transplant. Course of rituximab is repeated beginning on day 180 post-transplant.
  • Arm II (no rituximab): Patients receive G-CSF as in arm I. Patients are followed for 10 years.

PROJECTED ACCRUAL: A total of 427 patients will be accrued for this study within 3.5 years.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of diffuse large cell lymphoma and meeting the following criteria:

    • B-cell type with expression of CD20 either at diagnosis or at relapse
    • Relapse after having achieved an initial complete remission (CR) or failure to achieve initial CR (residual radiographic abnormalities after primary therapy allowed if these abnormalities are also positive by positron emission tomography or MRI [gallium])
    • No newly diagnosed disease
  • No progressive or stable disease to most recent salvage therapy

PATIENT CHARACTERISTICS:

Age

  • 18 to 70

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • AST or ALT < 3 times upper limit of normal

Renal

  • Creatinine ≤ 2.0 mg/dL OR
  • Creatinine clearance ≥ 40 mL/min

Cardiovascular

  • Cardiac ejection fraction ≥ 40%

Pulmonary

  • DLCO ≥ 60% of predicted

Other

  • No other malignancy within the past 2 years except basal cell skin cancer or carcinoma in situ of the cervix
  • No active infection requiring oral or IV antibiotics
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Chemotherapy
  • No more than 3 prior immunotherapy regimens

Chemotherapy

  • No more than 3 prior chemotherapy regimens

    • Addition of radiation or a monoclonal antibody to chemotherapy is considered one treatment regimen if the addition was part of the initial treatment plan
    • Addition of these therapies due to lack of response or poor response would be considered an additional treatment regimen whether given in front-line or salvage setting

Endocrine therapy

  • Not specified

Radiotherapy

  • See Chemotherapy
  • No more than 3 prior radiotherapy regimens
  • No prior radioimmunotherapy

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052923

Sponsors and Collaborators
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Investigators
Study Chair: Ian W. Flinn, MD, PhD Sidney Kimmel Comprehensive Cancer Center
Study Chair: Charles A. Linker, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00052923     History of Changes
Other Study ID Numbers: CDR0000258802, ECOG-E2499, CALGB-50205, CALGB-E2499
Study First Received: January 24, 2003
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014