Rituximab and Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Sponsor

University of Nebraska (Other)

Overall Status

Completed

CT.gov ID

NCT00007852

Collaborator

National Cancer Institute (NCI) (NIH), Genentech, Inc. (Industry)

Enrollment

Location

Arm

124

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. 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 or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of rituximab and combination chemotherapy followed by bone marrow or peripheral stem cell transplantation in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES: I. Determine the complete and partial response rate of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma treated with rituximab and high-dose carmustine, etoposide, cytarabine and melphalan followed by autologous bone marrow or peripheral blood stem cell transplantation. II. Determine the toxicity profile of this regimen in these patients. III. Compare the levels of soluble CD20 antigen and rituximab blood levels with patient outcomes in this patient population.

OUTLINE: Patients receive two doses of rituximab IV over 3-4 hours 1 week apart. Stem cells from the peripheral blood or bone marrow are collected at least 1 week after the second dose of rituximab. Following stem cell collection, patients receive a third dose of rituximab IV as above between days -10 and -6. Patients then receive high-dose chemotherapy consisting of carmustine IV on day -6, etoposide IV twice daily and cytarabine IV on days -5 to -2, and melphalan IV on day -1. On day 0 patients undergo autologous bone marrow or peripheral blood stem cell transplantation. After transplantation, patients receive a fourth dose of rituximab as above at approximately day 30, and then weekly over 4 weeks at approximately 6 months in the absence of disease progression or unacceptable toxicity. Patients are followed at 1 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 23-40 patients will be accrued for this study within 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Rituxan and BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Progenitor Transplant for Lymphoma

Study Start Date :

Sep 1, 2000

Actual Primary Completion Date :

Jan 1, 2002

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Rituxan and BEAM with autologous stem cell transplant	Biological: rituximab Rituximab at 375 mg/m2 administered approximately one week apart prior to collection of the hematopoietic stem cells. Rituxan at a dose of 375 mg/m2 IV will be given either on the days prior to initiation of the BCNU (days -10 to -7) or on the same day that the BCNU is administered for the BEAM chemotherapy regimen (Day -6). A fourth infusion of Rituxan 375 mg/m2 will be given at 30 day (+/- 20 days) post-transplant. At approximately 6 months post-transplant, if the patients have not had progressive lymphoma, they will receive four weekly doses of Rituxan 375 mg/m2 IV. Other Names: Rituxan Drug: carmustine BCNU 300 mg/M2 IV day -6 Other Names: BCNU Drug: cytarabine 100 mg/m2 on days -5 through -2 Other Names: BEAM chemotherapy regimen Drug: etoposide 100mg/M2 BID on days -5 through -2 Other Names: BEAM chemotherapy regimen Drug: melphalan 140 mg/m2 IV on day -1 Other Names: BEAM chemotherapy regimen Procedure: autologous hematopoietic stem cell transplantation Following the chemotherapy, on day 0 of treatment, the previously stored hematopoietic stem cells will be reinfused via the central venous line

Arm

Intervention/Treatment

Experimental: Arm I

Rituxan and BEAM with autologous stem cell transplant

Biological: rituximab

Rituximab at 375 mg/m2 administered approximately one week apart prior to collection of the hematopoietic stem cells. Rituxan at a dose of 375 mg/m2 IV will be given either on the days prior to initiation of the BCNU (days -10 to -7) or on the same day that the BCNU is administered for the BEAM chemotherapy regimen (Day -6). A fourth infusion of Rituxan 375 mg/m2 will be given at 30 day (+/- 20 days) post-transplant. At approximately 6 months post-transplant, if the patients have not had progressive lymphoma, they will receive four weekly doses of Rituxan 375 mg/m2 IV.

Other Names:

Rituxan

Drug: carmustine

BCNU 300 mg/M2 IV day -6

Other Names:

BCNU

Drug: cytarabine

100 mg/m2 on days -5 through -2

Other Names:

BEAM chemotherapy regimen

Drug: etoposide

100mg/M2 BID on days -5 through -2

Other Names:

BEAM chemotherapy regimen

Drug: melphalan

140 mg/m2 IV on day -1

Other Names:

BEAM chemotherapy regimen

Procedure: autologous hematopoietic stem cell transplantation

Following the chemotherapy, on day 0 of treatment, the previously stored hematopoietic stem cells will be reinfused via the central venous line

Outcome Measures

Primary Outcome Measures

The primary endpoint for this study is 100 day (complete + partial) response rate [100 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Diagnosis of CD20-positive B-cell non-Hodgkin's lymphoma Transplantation candidate Primary induction failure Chemotherapy refractory disease Received at least 3 prior chemotherapy regimens OR Diagnosis of mantle cell lymphoma No history of T-cell lymphoma No relapse or progression after rituximab therapy within 3 months before transplantation

PATIENT CHARACTERISTICS: Age: 19 and over Performance status: WHO 0-2 Life expectancy: At least 6 months Hematopoietic: Absolute neutrophil count at least 1,000/mm3* Platelet count more than 50,000/mm3* Hemoglobin more than 9.0 g/dL* *Unless due to lymphomatous involvement of the marrow Hepatic: Not specified Renal: Not specified Other: No serious disease or condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent corticosteroids except for transient control or prevention of nausea or vomiting Concurrent non-steroidal hormones for non-lymphoma-related conditions (e.g., insulin for diabetes) allowed Radiotherapy: No concurrent external beam radiotherapy during transplantation therapy Surgery: Not specified Other: No other concurrent antitumoral or investigational agents