Trial of Nonmyeloablative Conditioning With Fludarabine, Cyclophosphamide, and Total Body Irradiation Followed by Human Leukocyte Antigen (HLA)-Haploidentical or HLA-Identical Bone Marrow Transplantation, High-Dose Cyclophosphamide, and Rituximab for Patients With B-Cell Lymphoma

This study is currently recruiting participants.
Verified July 2012 by Sidney Kimmel Comprehensive Cancer Center

First Received on July 21, 2009.  
Last Updated on July 27, 2012  
History of Changes
This Clinical Trial Sponsored By: Sidney Kimmel Comprehensive Cancer Center
Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00946023

Purpose for Clinical Trial

This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient’s immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.

Condition Study Intervention Clinical Trial Phase
B-cell Lymphoma
Non Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Drug: Bone marrow transplantation Phase 2

Study Type: Study Interventional
Study Design: Endpoint Classification: Efficacy Study
Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Nonmyeloablative Allogeneic BMT for B-cell Lymphomas With Post-transplantation Cyclophosphamide and Rituximab and Optimized Donor Selection

Resource links provided by NLM:

MedlinePlus related topics:
Bone Marrow Transplantation
Chronic Lymphocytic Leukemia
Drug Information available for:
Fludarabine phosphate

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures For Clinical Trial:

  • Event-free survival [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures For Clinical Trial:

  • Longer-term event-free survival, overall survival, relapse, nonrelapse mortality, and incidence of acute and chronic graft versus host disease [ Time Frame: day 100, 1 year, 3 years ] [ Designated as safety issue: Yes ]
  • Feasibility of selecting donors based on favorable Fc receptor polymorphism status [ Time Frame: four years ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: July 2009
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)


Assigned Study Interventions

Experimental: Transplant Drug: Bone marrow transplantation

Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total body irradiation on day -1.

Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on day 0.

Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning day 30, rituximab IV is administered once per week for 8 weeks.

Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral mycophenolate mofetil until day 35 and tacrolimus (IV then changing to orally) until day 180.

Other Names:
  • rituximab
  • Rituxan
  • cyclophosphamide
  • Cytoxan
  • fludarabine
  • total body irradiation

Detailed Description:

This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Poor-risk CD20+, B-cell lymphoma, as follows:

    • Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion:

      1. Follicular grade 1 or 2 lymphoma
      2. Follicular lymphoma not otherwise specified
      3. Marginal zone (or MALT) lymphoma
      4. Lymphoplasmacytic lymphoma / Waldenstrom’s macroglobulinemia
      5. Hairy cell leukemia
      6. Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)
      7. Low grade B-cell lymphoma, unspecified
      8. Nodular lymphocyte-predominant Hodgkin lymphoma
  • Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or transformation

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