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

• ClinicalTrials.gov Identifier: NCT00007852
• Recruitment Status: Completed
• First Posted: February 12, 2004
• Last Update Posted: March 26, 2012
• Sponsor: University of Nebraska
• Collaborators: National Cancer Institute (NCI); Genentech, Inc.
• Information provided by (Responsible Party): Julie M Vose, MD, University of Nebraska

Tracking Information

• First Submitted Date: January 6, 2001
• First Posted Date: February 12, 2004
• Last Update Posted Date: March 26, 2012
• Study Start Date: September 2000
• Actual Primary Completion Date: January 2002 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 1, 2010): The primary endpoint for this study is 100 day (complete + partial) response rate [ Time Frame: 100 days ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rituximab and Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With 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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• 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 Name: Rituxan
• Drug: carmustine
  BCNU 300 mg/M2 IV day -6
  Other Name: BCNU
• Drug: cytarabine
  100 mg/m2 on days -5 through -2
  Other Name: BEAM chemotherapy regimen
• Drug: etoposide
  100mg/M2 BID on days -5 through -2
  Other Name: BEAM chemotherapy regimen
• Drug: melphalan
  140 mg/m2 IV on day -1
  Other Name: 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

Study Arms

Experimental: Arm I

Rituxan and BEAM with autologous stem cell transplant

Interventions:

• Biological: rituximab
• Drug: carmustine
• Drug: cytarabine
• Drug: etoposide
• Drug: melphalan
• Procedure: autologous hematopoietic stem cell transplantation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2010): 44
• Original Enrollment: Not Provided
• Actual Study Completion Date: January 2011
• Actual Primary Completion Date: January 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00007852
• Other Study ID Numbers: 045-00; P30CA036727 ( U.S. NIH Grant/Contract ); UNMC-045-00; NCI-V00-1634
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Julie M Vose, MD, University of Nebraska
• Study Sponsor: University of Nebraska

Collaborators

• National Cancer Institute (NCI)
• Genentech, Inc.

Investigators

• Study Chair: Julie M. Vose, MD; University of Nebraska

• PRS Account: University of Nebraska
• Verification Date: March 2012