Clinical Trial: Non-Myeloablative Conditioning and Bone Marrow Transplantation

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Disease and Other Hemoglobinopathies

Brief Summary: Allogeneic blood or marrow transplantation (alloBMT) is a curative therapy for a variety of hematologic disorders, including sickle cell disease and thalassemia. Even when it is clear that alloBMT can give to these patients an improvement in their disease, myeloablative transplants have important toxicities and mortalities associated. The lack of suitable donors continues to be a limit to access to transplantation. Substantial progress has been made recently in the development of pre-treatment regimens that facilitate the sustained engraftment of donor marrow with reduced toxicity. Most of these regimens incorporate highly immunosuppressive drugs, which allow the reduction or elimination of myeloablative agents or total body irradiation without endangering the sustained engraftment of HLA-identical allogeneic stem cells. Preliminary results of non-myeloablative allogeneic stem cell transplantation suggest that the procedure can be performed in patients who are ineligible for myeloablative alloBMT, and that sustained remissions of several hematologic malignancies can be obtained.

Detailed Summary:
Sponsor: Vanderbilt-Ingram Cancer Center

Current Primary Outcome: Transplant-related mortality (TRM) [ Time Frame: at 1 year after BMT ]

Defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Progression-free survival [ Time Frame: 2 years ]
    Development of grade II-IV acute graft-vs.-host disease, confirmed histologically by a pathologist.
  • Characterize donor hematopoietic chimerism in peripheral blood after mini-haploBMT [ Time Frame: at days ~30, ~60, and ~180 after mini-haploBMT ]

    Partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives. Defined in percentages of donor cells in patient's peripheral blood, measured in 4 ways.

    • Mixed donor chimerism: > 0% but < 95%
    • Complete donor chimerism > 95%

    Any amount of donor chimerism after day 60 will be considered as having engrafted

  • Characterize hematologic and non-hematologic toxicities of minihaploBMT [ Time Frame: Day 60 after BMT ]

    Hematologic toxicity:

    -Absolute neutrophil count (ANC): consecutive values of < 500/µL on 3 different days after chemotherapy post-BMT Platelet count: consecutive values of < 20,000 µL on 3 different days after chemotherapy post-BMT

    Non-hematologic toxicities:

    -Toxicities necessitating hospitalization Toxicities grade 4 or above

    Meets the criteria of the following SAE:

    • Relapse of underlying disease
    • Grade 3 ocular toxicity not related to ocular GVHD
    • Grade 3 related non-hematologic toxicity


Original Secondary Outcome: Same as current

Information By: Vanderbilt-Ingram Cancer Center

Dates:
Date Received: May 1, 2013
Date Started: May 2013
Date Completion: November 2017
Last Updated: January 9, 2017
Last Verified: January 2017