Trial record 1 of 1 for:    NCT00329030
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Rituxan vs Bexxar When Combined With Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) With Autologous Hematopoietic Stem Cell Transplantation (BMT CTN 0401)

This study has been completed.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00329030
First received: May 22, 2006
Last updated: June 10, 2016
Last verified: June 2016
  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:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
    Patients are considered a failure for this endpoint if they die, relapse/progress, or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (> 3cm). The time to this event is the time from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
    The event is death from any cause. The time to this event is the time from randomization to death or last follow-up. Surviving patients are censored at the time of last observation

  • Incidence of Relapse/Progression [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
    The time to this event is measured from randomization. Deaths without relapse/progression are considered as a competing risk. Surviving patients with no history of relapse/progression are censored at time of last follow-up.

  • Complete Response (CR) and Partial Response (PR) Proportion [ Time Frame: Day 100 and 2 years ] [ Designated as safety issue: No ]
  • Platelet Recovery to 20,000 Cells/μL [ Time Frame: 100 and 180 days ] [ Designated as safety issue: No ]
  • Hematologic Function [ Time Frame: 100 days, 1 year ] [ Designated as safety issue: No ]
    Hematologic function will be defined as ANC > 1,500 neutrophils/μL, hemoglobin > 10 g/dL without transfusion support, and platelet count > 100,000/μL without transfusion support.

  • Incidence of Infection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Mucositis Severity [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
    Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 equals severe mucosa.

  • Immune Reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Tests to be performed on peripheral blood include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-.

  • Immune Reconstitution of Quantitative Immunoglobulins [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Tests to be performed on peripheral blood for quantitative immunoglobulins include IgM, IgG and IgA.

  • Treatment-related Mortality (TRM) [ Time Frame: 1 and 2 years ] [ Designated as safety issue: Yes ]
    TRM is defined as death occurring in a patient from causes other than relapse or progression

  • Neutrophil Recovery [ Time Frame: Day 28 and Day 60 ] [ Designated as safety issue: Yes ]
    Time to neutrophil recovery will be the first of two consecutive days of > 500 neutrophils/μL following the expected nadir.


Enrollment: 224
Study Start Date: December 2005
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rituxan/BEAM
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); 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
Other Name: Rituximab
Experimental: Bexxar/BEAM
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); 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
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, 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).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
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 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
  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: NCT00329030

  Show 36 Study Locations
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Investigators
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
  More Information

Additional Information:
Publications:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00329030     History of Changes
Obsolete Identifiers: NCT00415012
Other Study ID Numbers: BMTCTN0401  BMT CTN 0401  U01HL069294-05  384 
Study First Received: May 22, 2006
Results First Received: January 28, 2016
Last Updated: June 10, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Findings will be published in a manuscript

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
Plasmablastic Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Large B-Cell, Diffuse
Etoposide
Etoposide phosphate
Iodine-131 anti-B1 antibody
Cytarabine
Melphalan
Rituximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2016