Rituximab & Combination Chemotherapy Followed by Transplantation in Relapsed or Refractory Non-Hodgkin's Lymphoma

NCT ID: NCT00007852

Last Updated: 2023-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-09-01
• Study Completion Date: 2011-01-01

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.

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Rituxan and BEAM with autologous stem cell transplant

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

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.

carmustine

Intervention Type: DRUG

BCNU 300 mg/M2 IV day -6

cytarabine

Intervention Type: DRUG

100 mg/m2 on days -5 through -2

etoposide

Intervention Type: DRUG

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

melphalan

Intervention Type: DRUG

140 mg/m2 IV on day -1

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

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

Interventions

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.

Intervention Type: BIOLOGICAL

carmustine

BCNU 300 mg/M2 IV day -6

Intervention Type: DRUG

cytarabine

100 mg/m2 on days -5 through -2

Intervention Type: DRUG

etoposide

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

Intervention Type: DRUG

melphalan

140 mg/m2 IV on day -1

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Other Intervention Names

Rituxan; BCNU; BEAM chemotherapy regimen; BEAM chemotherapy regimen; BEAM chemotherapy regimen

Eligibility Criteria

Inclusion Criteria

• 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
• Age 19 and over
• Performance status: WHO 0-2
• Life expectancy at least 6 months
• Absolute neutrophil count at least 1,000/mm3 (unless due to lymphomatous involvement of the marrow)
• Platelet count more than 50,000/mm3 (unless due to lymphomatous involvement of the marrow)
• Hemoglobin more than 9.0 g/dL (unless due to lymphomatous involvement of the marrow)
• Fertile patients must use effective contraception
• Concurrent non-steroidal hormones for non-lymphoma-related conditions (e.g., insulin for diabetes) allowed

Exclusion Criteria

• No other concurrent chemotherapy
• No concurrent corticosteroids except for transient control or prevention of nausea or vomiting
• No concurrent external beam radiotherapy during transplantation therapy
• No other concurrent antitumoral or investigational agents
• No history of T-cell lymphoma
• No relapse or progression after rituximab therapy within 3 months before transplantation
• No serious disease or condition that would preclude study
• Not pregnant or nursing/negative pregnancy test

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie M Vose, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-V00-1634

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

0045-00-FB

Identifier Type: -

Identifier Source: org_study_id