Clinical trial NCT00007852: Rituximab & Combination Chemotherapy Followed by Transplantation in Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase II Trial of Rituxan and BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Progenitor Transplant for Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Genentech, Inc.
First posted: 2004-02-12
Enrollment: 44
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 100 day (complete + partial) response rate
timeFrame: 100 days
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Julie M Vose, MD
role: PRINCIPAL_INVESTIGATOR
References: