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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00946023
First received: July 21, 2009
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

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

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

Resource links provided by NLM:


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

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

Secondary Outcome Measures:
  • 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 ]

Enrollment: 135
Study Start Date: July 2009
Estimated Study Completion Date: August 2015
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned 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.

  Eligibility

Ages Eligible for Study:   1 Year to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00946023

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

Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00946023     History of Changes
Other Study ID Numbers: J0941, NA_00025589
Study First Received: July 21, 2009
Last Updated: September 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
lymphoma
non hodgkin lymphoma
allogeneic
bone marrow transplantation
nonmyeloablative
cyclophosphamide
rituximab

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

ClinicalTrials.gov processed this record on April 17, 2014