Randomized Phase III Trial Of Rituximab (NSC #687451) And Autologous Stem Cell Transplantation For B Cell Diffuse Large Cell Lymphoma


Phase 3
18 Years
70 Years
Not Enrolling
Both
Lymphoma

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Trial Information

Randomized Phase III Trial Of Rituximab (NSC #687451) And Autologous Stem Cell Transplantation For B Cell Diffuse Large Cell Lymphoma


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:

No

Principal Investigator

Ian W. Flinn, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000258802

NCT ID:

NCT00052923

Start Date:

March 2003

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent adult diffuse large cell lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin

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