Know Cancer

or
forgot password

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)


Phase 3
18 Years
80 Years
Open (Enrolling)
Both
Lymphoma, B-Cell, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, Non-Hodgkin

Thank you

Trial Information

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)


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).


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

2 and 3 years

Safety Issue:

No

Principal Investigator

Edward Ball, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Diego

Authority:

United States: Food and Drug Administration

Study ID:

384

NCT ID:

NCT00329030

Start Date:

December 2005

Completion Date:

August 2014

Related Keywords:

  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Non-Hodgkin
  • Large B-Cell Lymphoma
  • Non-Hodgkin's Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Pennsylvania Cancer CenterPhiladelphia, Pennsylvania  19104
Medical University of South CarolinaCharleston, South Carolina  29425-0721
University of California Davis Medical CenterSacramento, California  95817
Loyola University Medical CenterMaywood, Illinois  60153
Medical College of WisconsinMilwaukee, Wisconsin  53226
University of Rochester Medical CenterRochester, New York  14642
Hackensack University Medical CenterHackensack, New Jersey  07601
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Cancer Centers of the CarolinasGreenville, South Carolina  29605
Baylor University Medical CenterDallas, Texas  75246
Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
University of MinnesotaMinneapolis, Minnesota  55455
Duke University Medical CenterDurham, North Carolina  27710
University of Michigan Medical CenterAnn Arbor, Michigan  48104-0914
H. Lee Moffitt Cancer CenterTampa, Florida  33612
Emory UniversityAtlanta, Georgia  30322
Providence Portland Medical CenterPortland, Oregon  97213-3635
University of Texas Southwestern Medical CenterDallas, Texas  
Wichita CCOPWichita, Kansas  67214-3882
Texas Transplant InstituteSan Antonio, Texas  78229
University of California, San Diego Medical CenterSan Diego, California  
University of MiamiMiami, Florida  33136
University of NebraskaOmaha, Nebraska  68198
Yale University School Of MedicineNew Haven, Connecticut  06520
University of Florida College of Medicine (Shands)Gainesville, Florida  32610
Johns Hopkins/SKCCCBaltimore, Maryland  21231
Washington University/Barnes Jewish HospitalSt. Louis, Missouri  63110
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
University Hospitals of Cleveland/Case WesternCleveland, Ohio  44106
University of Oklahoma Medical CenterOklahoma City, Oklahoma  73104
Columbia River Oncology ProgramPortland, Oregon  97225
Tufts-New England Medical CenterBoston, Massachusetts  02111
St. Lukes Mountain States Tumor InstituteBoise, Idaho  83712
University of Maryland Medical Systems/Greenbaum Cancer CenterBaltimore, Maryland  21228
Cancer Institute of New Jersey, Robert Wood Johnson UniversityNew Brunswick, New Jersey  08903
Weill Cornell Medical College, The New York Presbyterian HospitalNew York, New York  10065
University of North Carolina Hospital at Chapel HillChapel Hill, North Carolina  27599
Intermountain BMT ProgramSalt Lake City, Utah  84143
University of Utah Medical School, BMTSalt Lake City, Utah  84132
Virginia Commonwealth University/MCV HospitalRichmond, Virginia  23298