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

Purpose

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	Intervention	Phase
Lymphoma	Biological: rituximab Drug: carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation	Phase 2


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Rituximab

Genetic and Rare Diseases Information Center resources: Burkitt Lymphoma Lymphosarcoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Marginal Zone Lymphoma B-cell Lymphoma Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Lymphoma, Large-cell Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic

U.S. FDA Resources

Further study details as provided by Julie M Vose, MD, University of Nebraska:

Primary Outcome Measures:

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


Enrollment:	44
Study Start Date:	September 2000
Study Completion Date:	January 2011
Primary Completion Date:	January 2002 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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

Arms

Assigned Interventions

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 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

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


Ages Eligible for Study:	19 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00007852

Locations


United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3330

Sponsors and Collaborators

University of Nebraska

National Cancer Institute (NCI)

Genentech, Inc.

Investigators


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

More Information


Responsible Party:	Julie M Vose, MD, Professor & N/M Harris Oncology Professorship, University of Nebraska
ClinicalTrials.gov Identifier:	NCT00007852 History of Changes
Other Study ID Numbers:	045-00 P30CA036727 ( U.S. NIH Grant/Contract ) UNMC-045-00 NCI-V00-1634
Study First Received:	January 6, 2001
Last Updated:	March 23, 2012

Keywords provided by Julie M Vose, MD, University of Nebraska:


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

Additional relevant MeSH terms:


Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Rituximab Etoposide Cytarabine Melphalan Carmustine Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs	Antirheumatic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists

ClinicalTrials.gov processed this record on September 21, 2017