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

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) Cancer and Leukemia Group B
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00052923

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Etoposide Etoposide phosphate Filgrastim Rituximab Carmustine

U.S. FDA Resources

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

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

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Cancer and Leukemia Group B

Investigators

Study Chair:	Ian W. Flinn, MD, PhD	Sidney Kimmel Comprehensive Cancer Center
Study Chair:	Charles A. Linker, MD	UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

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

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Lymphoma, B-Cell
Therapeutic Uses
Lymphoma
Etoposide
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Neoplasms by Histologic Type

Immune System Diseases
Rituximab
Carmustine
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on November 27, 2009