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Lymphoma, B-CellPhase 3NCT00329030

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

A Phase 3 study testing Autologous transplantation using rituxan/BEAM and Autologous transplantation using Bexxar/BEAM in people with Lymphoma, B-Cell and Lymphoma, Large-Cell, Immunoblastic, run by National Heart, Lung, and Blood Institute (NHLBI) at 36 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Autologous transplantation using rituxan/BEAM and Autologous transplantation using Bexxar/BEAM
Could I receive a placebo?
No, everyone receives an active treatment
How many people
224 participants
Where
36 sitesUnited States
Study dates
Dec 2005to Aug 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

36 sites in 1 country.

36 sites in 1 country

United States36 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • University of Maryland Medical Systems/Greenbaum Cancer Center

    Baltimore, Maryland, 21228

  • Johns Hopkins/SKCCC

    Baltimore, Maryland, 21231

  • St. Lukes Mountain States Tumor Institute

    Boise, Idaho, 83712

  • Tufts-New England Medical Center

    Boston, Massachusetts, 02111

  • University of North Carolina Hospital at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University Hospitals of Cleveland/Case Western

    Cleveland, Ohio, 44106

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • University of Florida College of Medicine (Shands)

    Gainesville, Florida, 32610

  • Cancer Centers of the Carolinas

    Greenville, South Carolina, 29615

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • University of Miami

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53211

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University School of Medicine

    New Haven, Connecticut, 06520

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

  • Weill Cornell Medical College, The New York Presbyterian Hospital

    New York, New York, 10065

  • University of Nebraska

    Omaha, Nebraska, 68198

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Columbia River Oncology Program

    Portland, Oregon, 97225

  • Virginia Commonwealth University/MCV Hospital

    Richmond, Virginia, 23298

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • University of Utah Medical School, BMT

    Salt Lake City, Utah, 84132

  • Intermountain BMT Program

    Salt Lake City, Utah, 84143

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University/Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

Other trials in United States

About this study

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 (BMTCTN0401)

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.

Read the 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).

Being tested
Autologous transplantation using rituxan/BEAM, Autologous transplantation using Bexxar/BEAM
Keywords
Large B-Cell Lymphoma, Non-Hodgkin's Lymphoma
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous transplantation using rituxan/BEAMDrug

    Also called Rituximab

    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

  • Autologous transplantation using Bexxar/BEAMDrug

    Also called Tositumomab and Iodine I 131 Tositumomab Bexxar

    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

Study groups in NCT00329030
Study groupRoleWhat they receive
Rituxan/BEAMActive comparatorAutologous transplantation using rituxan/BEAM
Receives: Drug: Autologous transplantation using rituxan/BEAM
Bexxar/BEAMExperimentalAutologous transplantation using Bexxar/BEAM
Receives: Drug: Autologous transplantation using Bexxar/BEAM

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 and 2 years

Secondary outcomes (11)

  1. Overall Survival

    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

    Measured: 1 and 2 years

  2. Incidence of Relapse/Progression

    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.

    Measured: 1 and 2 years

  3. Complete Response (CR) and Partial Response (PR) Proportion

    Measured: Day 100 and 2 years

  4. Platelet Recovery to 20,000 Cells/μL

    Measured: 100 and 180 days

  5. Hematologic Function

    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.

    Measured: 100 days, 1 year

  6. Incidence of Infection

    Measured: 1 year

  7. Mucositis Severity

    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.

    Measured: Day 21

  8. Immune Reconstitution

    Tests to be performed on peripheral blood include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-.

    Measured: 1 year

  9. Immune Reconstitution of Quantitative Immunoglobulins

    Tests to be performed on peripheral blood for quantitative immunoglobulins include IgM, IgG and IgA.

    Measured: 1 year

  10. Treatment-related Mortality (TRM)

    TRM is defined as death occurring in a patient from causes other than relapse or progression

    Measured: 1 and 2 years

  11. Neutrophil Recovery

    Time to neutrophil recovery will be the first of two consecutive days of > 500 neutrophils/μL following the expected nadir.

    Measured: Day 28 and Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2006 (estimated)
  2. Study startDec 2005
  3. Primary completionAug 2013
  4. Study completionAug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
224 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00329030
Sponsor's protocol ID
BMTCTN0401
Other IDs
BMT CTN 0401, U01HL069294-05, 384
Status last verified
Aug 2017
First submitted
22 May 2006
Last updated
1 Nov 2021
Data monitoring committee
Yes
Individual data sharing
Yes: 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).

Publications

  • 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.

    PubMed 23478060

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Autologous transplantation using rituxan/BEAM and Autologous transplantation using Bexxar/BEAM in people with Lymphoma, B-Cell and Lymphoma, Large-Cell, Immunoblastic, run by National Heart, Lung, and Blood Institute (NHLBI) at 36 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: 1 and 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00329030, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021; AzTrials last refreshed its copy on 7 Nov 2026.

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