Comparison of Rituxan Versus Bexxar When Combined With Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) With Autologous Hematopoietic Stem Cell Transplantation (ASCT) (BMT CTN 0401)
This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00329030
First received: May 22, 2006
Last updated: January 12, 2012
Last verified: January 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma, B-Cell Lymphoma, Large-Cell, Immunoblastic Lymphoma, Non-Hodgkin |
Drug: Autologous transplantation using rituxan/BEAM Drug: Autologous transplantation using Bexxar/BEAM |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase III Rituxan/BEAM vs. Bexxar/BEAM With Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-cell Non-Hodgkin's Lymphoma (BMT CTN #0401) |
Resource links provided by NLM:
Drug Information available for:
Cytarabine
Melphalan
Iodine
Sodium iodide I 131
Iodide
Etoposide
Rituximab
Tositumomab
U.S. FDA Resources
Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):
Primary Outcome Measures:
- Progression-free survival (PFS) after autologous hematopoietic stem cell transplantation (ASCT) for chemotherapy-sensitive diffuse large B-cell lymphoma using Rituxan/BEAM versus Bexxar/BEAM for pre-transplant conditioning [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall survival [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
- Complete response (CR) and partial response (PR) proportion at Day 100 [ Time Frame: Day 100, 2 years ] [ Designated as safety issue: No ]
- Time to hematopoietic recovery [ Time Frame: 100 days, 1 year ] [ Designated as safety issue: No ]
- Hematologic function [ Time Frame: 100 days, 1 year ] [ Designated as safety issue: No ]
- Incidence of infection [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
- Maximum mucositis score by Day 21 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
- Immune reconstitution [ Time Frame: Day 100, 1 year, 2 years ] [ Designated as safety issue: No ]
- Transplant-related mortality [ Time Frame: 100 days, 6 months ] [ Designated as safety issue: Yes ]
- Development of myelodysplasia/AML/abnormal cytogenetics [ Time Frame: 1, 2 and 5 years ] [ Designated as safety issue: Yes ]
- Primary graft failure [ Time Frame: Day 21, Day 42 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 224 |
| Study Start Date: | December 2005 |
| Estimated Study Completion Date: | August 2014 |
| Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Autologous transplantation using rituxan/BEAM
|
Drug: Autologous transplantation using rituxan/BEAM
Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); VP-16 100 mg/m2 BID (Days -5 to -2); Cytarabine 100 mg/m2 BID (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Name: Rituximab
|
|
Experimental: 2
Autologous transplantation using Bexxar/BEAM
|
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); VP-16 100 mg/m2 BID (Days -5 to -2); Cytarabine 100 mg/m2 BID (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Name: Tositumomab and Iodine I 131 Tositumomab Bexxar
|
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, 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).
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 MUGA
- Hepatic: Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and ALT and 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: DLCO, FEV1, 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 HSCT
- Patients with evidence of 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 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00329030
Show 44 Study Locations
Show 44 Study LocationsSponsors and Collaborators
Blood and Marrow Transplant Clinical Trials Network
Investigators
| Principal Investigator: | Edward Ball, MD | University of California, San Diego |
| Principal Investigator: | Stuart Seropian, MD | Yale University |
| Principal Investigator: | John Wingard, MD | University of Florida College of Medicine (Shands) |
| Principal Investigator: | Ernesto Ayala, MD | H. Lee Moffitt Cancer Center |
| Principal Investigator: | Mary Jo Lechowicz, MD | Emory University |
| Principal Investigator: | Margarida Silverman, MD | University of Iowa |
| Principal Investigator: | Saul Yanovich, MD | University of Maryland Medical Systems/Greenbaum Cancer Center |
| Principal Investigator: | John Koreth, MD | DFCI/Brigham & Women's Hospital |
| Principal Investigator: | Shin Mineishi, MD | University of Michigan |
| Principal Investigator: | Linda Burns, MD | University of Minnesota - Clinical and Translational Science Institute |
| Principal Investigator: | John DiPersio, MD, PhD | Washington University/Barnes Jewish Hospital |
| Study Chair: | Julie Vose, MD | University of Nebraska |
| Principal Investigator: | Scott Rowley, MD | Hackensack University Medical Center |
| Principal Investigator: | Nelson Chao, MD | Duke University Medical Center (Adults) |
| Principal Investigator: | Hillard Lazarus, MD | University Hospitals of Cleveland/Case Western |
| Principal Investigator: | Steve Schuster, MD | University of Pennsylvania |
| Principal Investigator: | Gary Spitzer, MD | Cancer Centers of the Carolinas |
| Principal Investigator: | Edward Agura, MD | Baylor Health Care System |
| Principal Investigator: | Paul Shaughnessy, MD | Texas Transplant Institute |
| Principal Investigator: | Harold Chung, MD | Virginia Commonwealth University/MCV Hospital |
| Principal Investigator: | Timothy Fenske, MD | Medical College of Wisconsin |
| Principal Investigator: | Keith Lanier, MD | Columbia River Oncology Program |
| Principal Investigator: | Oliver Press, MD | Fred Hutchinson Cancer Research Center |
| Principal Investigator: | Robert Chapman, MD | Henry Ford Health System |
| Principal Investigator: | Richard Ambinder, MD, PhD | Johns Hopkins/SKCCC |
| Principal Investigator: | James Wade, MD, MPH | Medical College of Wisconsin |
| Principal Investigator: | Tarun Kewalramani, MD | Memorial Sloan-Kettering Cancer Center |
| Principal Investigator: | Christopher Reynolds, MD | Providence Health & Services |
| Principal Investigator: | Philip McCarthy, MD | Roswell Park Cancer Institute |
| Principal Investigator: | Andreas Klein, MD | Tufts Medical Center |
| Principal Investigator: | Denise Pereira, MD | University of Miami |
| Principal Investigator: | George Selby, MD | University of Oklahoma Medical Center |
| Principal Investigator: | Walter Longo, MD | University of Wisconsin Hospital and Clinics |
| Principal Investigator: | Stacey Goodman, MD | Vanderbilt University |
| Principal Investigator: | David Hurd, MD | Wake Forest University |
| Principal Investigator: | Arnold Rubin, MD | Cancer Institute of New Jersey |
| Principal Investigator: | Clyde D Ford, MD | Intermountain BMT Program |
| Principal Investigator: | David Vesole, MD | Loyola University |
| Principal Investigator: | Robert Stuart, MD | Medical University of South Carolina |
| Principal Investigator: | Henry CH Fung, MD | Rush University |
| Principal Investigator: | William H Kreisle, MD | St. Lukes Mountain States Tumor Institute |
| Principal Investigator: | Carol Richman, MD | Univeristy of California Davis Medical Center |
| Principal Investigator: | Joseph McGuirk, MD | University of Kansas Hospital |
| Principal Investigator: | Thomas C Shea, MD | University of North Carolina Hospital at Chapel Hill |
| Principal Investigator: | Jonathan Friedberg, MD | University of Rochester |
| Principal Investigator: | Madhuri Vusirikala, MD | University of Texas Southwestern Medical Center |
| Principal Investigator: | Michael Pulsipher, MD | Utah BMT, University of Utah Medical School |
| Principal Investigator: | Tsiporah B Shore, MD | Weill Cornell Medical College, The New York Presbyterian Hospital |
| Principal Investigator: | Shaker R Dakhil, MD | Wichita CCOP |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Heart, Lung, and Blood Institute (NHLBI) |
| ClinicalTrials.gov Identifier: | NCT00329030 History of Changes |
| Obsolete Identifiers: | NCT00415012 |
| Other Study ID Numbers: | 384, BMT CTN 0401, U01 HL069294-05 |
| Study First Received: | May 22, 2006 |
| Last Updated: | January 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
|
Large B-Cell Lymphoma Non-Hodgkin's Lymphoma |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large-Cell, Immunoblastic Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Rituximab Iodine-131 anti-B1 antibody |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 19, 2013