NCT00329030

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
224

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Dec 2005

Longer than P75 for phase_3

Geographic Reach
1 country

36 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2005

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

May 22, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 24, 2006

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

June 10, 2016

Completed
Last Updated

November 1, 2021

Status Verified

August 1, 2017

Enrollment Period

7.7 years

First QC Date

May 22, 2006

Results QC Date

January 28, 2016

Last Update Submit

October 21, 2021

Conditions

Keywords

Large B-Cell LymphomaNon-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS)

    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.

    1 and 2 years

Secondary Outcomes (11)

  • Overall Survival

    1 and 2 years

  • Incidence of Relapse/Progression

    1 and 2 years

  • Complete Response (CR) and Partial Response (PR) Proportion

    Day 100 and 2 years

  • Platelet Recovery to 20,000 Cells/μL

    100 and 180 days

  • Hematologic Function

    100 days, 1 year

  • +6 more secondary outcomes

Study Arms (2)

Rituxan/BEAM

ACTIVE COMPARATOR

Autologous transplantation using rituxan/BEAM

Drug: Autologous transplantation using rituxan/BEAM

Bexxar/BEAM

EXPERIMENTAL

Autologous transplantation using Bexxar/BEAM

Drug: Autologous transplantation using Bexxar/BEAM

Interventions

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

Also known as: Rituximab
Rituxan/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

Also known as: Tositumomab and Iodine I 131 Tositumomab Bexxar
Bexxar/BEAM

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Florida College of Medicine (Shands)

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

St. Lukes Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Maryland Medical Systems/Greenbaum Cancer Center

Baltimore, Maryland, 21228, United States

Location

Johns Hopkins/SKCCC

Baltimore, Maryland, 21231, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Weill Cornell Medical College, The New York Presbyterian Hospital

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Cancer Centers of the Carolinas

Greenville, South Carolina, 29615, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

University of Utah Medical School, BMT

Salt Lake City, Utah, 84132, United States

Location

Intermountain BMT Program

Salt Lake City, Utah, 84143, United States

Location

Virginia Commonwealth University/MCV Hospital

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Lymphoma, B-CellLymphoma, Large-Cell, ImmunoblasticLymphoma, Non-Hodgkin

Interventions

Rituximabtositumomab I-131

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Adam Mendizabal
Organization
The EMMES Corporation

Study Officials

  • Mary Horowitz, MD

    Center for International Blood and Marrow Transplant Research

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 22, 2006

First Posted

May 24, 2006

Study Start

December 1, 2005

Primary Completion

August 1, 2013

Study Completion

August 1, 2013

Last Updated

November 1, 2021

Results First Posted

June 10, 2016

Record last verified: 2017-08

Data Sharing

IPD Sharing
Will share

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
Within 6 months of official study closure at participating sites.
Access Criteria
Available to the public
More information

Locations