Rapamycin for Immunosuppression and B Cell Modulation Post Stem Cell Transplant for Acute Lymphoblastic Leukemia (ALL)
Primary objective: Evaluate toxicity of rapamycin when used for post-bone marrow transplant graft vs. host disease prophylaxis in children with acute lymphoblastic leukemia (ALL).
Investigator initiated; four participating institutions; Phase II pilot study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||CHP-753, Rapamycin for Immunosuppression and B Cell Modulation Post Stem Cell Transplant for Acute Lymphoblastic Leukemia (ALL)|
- Number of Participants With Transplant-related Mortality [ Time Frame: 24 months after transplant ] [ Designated as safety issue: Yes ]Death not associated with relapse. We determined that if transplant related mortality(TRM) 25% at day 100 or if Grade III-IV (severe, life threatening, or disabling) acute GVHD was >30% a stopping rule would be triggered.
- Two Year Overall Survival [ Time Frame: 24 months after transplant ] [ Designated as safety issue: Yes ]The probability that a given patient will be alive two years after transplantation. The Kaplan-Meier product limit method was used to compute the probability of overall survival to 2 years. Greenwood's formula was used to compute the standard error.
- Percentage of Patients Developing Acute Graft vs. Host Disease (GVHD) [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]Cumulative incidence of Grade 2-4 acute GVHD at 180 days.
|Study Start Date:||August 2005|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
|Experimental: All participants||
Rapamycin (RAPA, RapamuneR) (sirolimus) is an immunosuppressive agent that was approved by the FDA in 1999. It is a macrocyclic lactone that is structurally similar to Tacrolimus (FK506) and binds to the same intracellular protein as FK506, FKBP1,2,3, but it has an entirely different mechanism of action and a different principal target protein. The target of the RAPA: FKBP complex is the mammalian target of rapamycin (mTOR). Unlike the calcineurin inhibitors cyclosporine (CSA) and - FK506, RAPA exerts its effects by inhibiting growth factor-driven transduction signals in the T-cell response to alloantigen, thus preventing proliferation among T and B lymphocytes3,4.
Other Name: (RAPA, RapamuneR) (sirolimus)
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|United States, Utah|
|Primary Children's Medical Center|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Michael Pulsipher, MD||Primary Children's Medical Center|