Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin's Lymphoma (BMTCTN0401)

NCT ID: NCT00329030

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2013-08-31

Brief Summary

This study is designed as a Phase III, multicenter trial, comparing progression-free survival (PFS) after autologous hematopoietic stem cell transplantation using a standard Rituxan plus BEAM transplant regimen versus a regimen adding Bexxar to BEAM.

Detailed Description

BACKGROUND:

Bexxar (Tositumomab and Iodine I 131 Tositumomab) is a radioimmunoconjugate with demonstrated anti-lymphoma effects. This drug is indicated for the treatment of patients with CD20 positive, relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. Bexxar has been used in several Phase I and II transplant trials either alone or in combination with high-dose chemotherapy for the treatment of relapsed non-Hodgkin's lymphoma. The Phase I and II trials combining Bexxar with BEAM and autologous hematopoietic stem cell transplantation demonstrated promising early results with 80% event-free survival in relapsed chemosensitive diffuse large B-cell non-Hodgkin's lymphoma patients. The administration of Rituxan to the mobilization and conditioning regimen is now the standard of care at most transplant centers. Therefore, the primary endpoint of this study will be to compare progression-free survival after autologous hematopoietic stem cell transplantation for chemotherapy-sensitive diffuse large B-cell lymphoma using Rituxan/BEAM versus Bexxar/BEAM for pre-transplant conditioning.

DESIGN NARRATIVE:

All patients will receive induction or salvage chemotherapy as indicated by their clinical circumstance to achieve at least a partial response (as defined in the protocol). There must be 20% or less bone marrow involvement after their most recent salvage therapy.

Mobilization therapy may be employed per institutional guidelines, but all patients must receive one dose of rituxan (375 mg/m^2) at least within 4 weeks of actual stem cell apheresis. Patients must have an adequate autograft (target of at least 2.0 X 10^6 CD34+ cells/kg; minimum of more than 1.5 X 106 CD34+ cells/kg) to be eligible for the protocol. Eligible patients will be randomized to receive either: 1) Rituxan plus BEAM, with Rituxan 375 mg/m^2 IV Days -19 and -12, Carmustine (BCNU) 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT; or, 2) Bexxar/BEAM with the dosimetric dose of 5 mCi Bexxar on Day -19 and the therapeutic dose calculated to administer 75 cGy total body dose (TBD) on Day -12. Patients will then receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT.

Patients will be followed for 2 years post-transplant. Survival data, hematopoiesis data, incidence of infection, mucositis assessment data, immune reconstitution data, and toxicity data will be recorded and reported periodically to the BMT CTN Data Coordinating Center (DCC).

Conditions

Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin

Keywords

Large B-Cell Lymphoma; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituxan/BEAM

Autologous transplantation using rituxan/BEAM

Group Type: ACTIVE_COMPARATOR

Autologous transplantation using rituxan/BEAM

Intervention Type: DRUG

Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation

Bexxar/BEAM

Autologous transplantation using Bexxar/BEAM

Group Type: EXPERIMENTAL

Autologous transplantation using Bexxar/BEAM

Intervention Type: DRUG

Bexxar dosimetric dose 5 mCi (Day -19); Bexxar therapy dose 75 cGy TBD (Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation

Interventions

Autologous transplantation using rituxan/BEAM

Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation

Intervention Type: DRUG

Autologous transplantation using Bexxar/BEAM

Bexxar dosimetric dose 5 mCi (Day -19); Bexxar therapy dose 75 cGy TBD (Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation

Intervention Type: DRUG

Other Intervention Names

Rituximab; Tositumomab and Iodine I 131 Tositumomab Bexxar

Eligibility Criteria

Inclusion Criteria

• Diagnosis of persistent or recurrent REAL classification diffuse large B-cell lymphoma, composite lymphoma with more than 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma
• Demonstration of CD20+ on at least one histologic specimen
• 18-80 years old at time of first registration
• Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies); monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies
• Disease status of primary induction failure, first relapse, or second complete remission; all patients must have chemosensitive disease as demonstrated by response to induction or salvage chemotherapy with at least a partial response (as defined in the protocol)
• No more than a 20% bone marrow involvement
• Patients with adequate organ function as measured by:
• Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients greater than 60 years of age must have a left ventricular ejection fraction at rest of at least 40% demonstrated by Multi-Gated Acquisition Scan (MUGA)
• Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3x the upper limit of normal
• Renal: Creatinine less than 2.0 mg/dL or creatinine clearance (calculated creatinine clearance is permitted) more than 40 mL/min; no hydronephrosis on CT scan prior to mobilization
• Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), Volume forcibly exhaled in one second (FEV1), forced vital capacity (FVC) at least 45% of predicted (corrected for hemoglobin)
• Autologous graft with a minimum of at least 1.5 X 10^6 CD34+ cells/kg (target greater than 2.0 X 10^6 CD34+ cells/kg. Peripheral blood stem cells (PBSC) are preferred; however, if PBSC mobilization fails, cells can be obtained by institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional practice for total nucleated cell dose should be used).
• Initiate conditioning therapy within 3 months of mobilization
• Signed informed consent

Exclusion Criteria

• Karnofsky performance score less than 70%
• Transformed follicular lymphoma
• Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement)
• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with curative intent less than 5 years previously will be allowed
• Pregnant (positive β-HCG) or breastfeeding; this patient population is excluded due to the lack of data on the use of Bexxar in patients who are pregnant or breastfeeding
• Seropositivity for HIV; this patient population is excluded due to the lack of data on the use of Bexxar in HIV positive patients and because the treatment regimens are too immunosuppressive for this patient population
• Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant
• Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
• Patients with evidence of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination
• Patients with a prior severe reaction to Rituxan or Filgrastim (G-CSF). Patients with severe reactions to G-CSF that receive pre-medication for control of the reaction are not excluded from study.
• Patients who have received prior radioimmunotherapy
• Patients with known hypersensitivity to murine proteins

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

Yale University School of Medicine

New Haven, Connecticut, United States

University of Florida College of Medicine (Shands)

Gainesville, Florida, United States

University of Miami

Miami, Florida, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

St. Lukes Mountain States Tumor Institute

Boise, Idaho, United States

Loyola University Medical Center

Maywood, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Maryland Medical Systems/Greenbaum Cancer Center

Baltimore, Maryland, United States

Johns Hopkins/SKCCC

Baltimore, Maryland, United States

Tufts-New England Medical Center

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University/Barnes Jewish Hospital

St Louis, Missouri, United States

University of Nebraska

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College, The New York Presbyterian Hospital

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Columbia River Oncology Program

Portland, Oregon, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Cancer Centers of the Carolinas

Greenville, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor University Medical Center

Dallas, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

University of Utah Medical School, BMT

Salt Lake City, Utah, United States

Intermountain BMT Program

Salt Lake City, Utah, United States

Virginia Commonwealth University/MCV Hospital

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. doi: 10.1200/JCO.2012.45.9453. Epub 2013 Mar 11.

Reference Type: RESULT

PMID: 23478060 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

BMT CTN 0401

Identifier Type: OTHER

Identifier Source: secondary_id

U01HL069294-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

384

Identifier Type: OTHER

Identifier Source: secondary_id

BMTCTN0401

Identifier Type: -

Identifier Source: org_study_id

NCT00415012

Identifier Type: -

Identifier Source: nct_alias