Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00946023
Recruitment Status : Terminated
First Posted : July 24, 2009
Last Update Posted : September 24, 2013
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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 or disease Intervention/treatment Phase
Lymphoma B-cell Lymphoma Non Hodgkin Lymphoma Chronic Lymphocytic Leukemia Drug: Bone marrow transplantation Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 135 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas
Study Start Date : July 2009
Actual Primary Completion Date : July 2013
Estimated Study Completion Date : August 2015

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Event-free survival [ Time Frame: one year ]

Secondary Outcome Measures :
  1. 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 ]
  2. Feasibility of selecting donors based on favorable Fc receptor polymorphism status [ Time Frame: four years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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 (if histologic conversion, PR or CR is required):

      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 histologic conversion (if histologic conversion, PR or CR is required)
  • Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR or CR, and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:

    1. Follicular grade 3 lymphoma
    2. Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma
    3. Mantle cell lymphoma
    4. Diffuse large B-cell lymphoma (excluding primary CNS lymphoma)
    5. "Gray zone" or composite lymphomas with combined features of primary mediastinal large B-cell and Hodgkin's lymphoma
    6. Burkitt's lymphoma/leukemia
    7. Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)
  • Must have a related donor who is at least HLA haploidentical
  • Any previous BMT must have occurred at least 3 months prior
  • Left ventricular ejection fraction at least 35%
  • Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT and AST no more than 5 x upper limit of normal
  • FEV1 and FVC at least 40% of predicted
  • Absence of uncontrolled infection

Exclusion Criteria:

  • More than 20% involvement of bone marrow by chronic lymphocytic leukemia
  • Active central nervous system lymphoma
  • ECOG performance status greater than 1 (2,3, and 4)
  • HIV positive
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00946023

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Principal Investigator: Yvette L Kasamon, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00946023     History of Changes
Other Study ID Numbers: J0941
NA_00025589 ( Other Identifier: Johns Hopkins Medicine Institutional Review Board )
First Posted: July 24, 2009    Key Record Dates
Last Update Posted: September 24, 2013
Last Verified: September 2013

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
non hodgkin lymphoma
bone marrow transplantation

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists