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

University of Nebraska

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Procedure: autologous hematopoietic stem cell transplantation

Drug: cytarabine

Drug: etoposide

Biological: rituximab

Drug: carmustine

Drug: melphalan

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00007852

NCI-V00-1634

P30CA036727 (U.S. NIH Grant/Contract)

0045-00-FB

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

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