Rapamycin for Immunosuppression and B Cell Modulation Post Stem Cell Transplant for Acute Lymphoblastic Leukemia (ALL)

This study has been completed.
Sponsor:
Collaborator:
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00795886
First received: November 19, 2008
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

Objectives:

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


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: RAPAMYCIN
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 63
Study Start Date: August 2005
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All participants Drug: RAPAMYCIN
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)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Pediatric patients' ages (0 - 21 years) with lymphoid malignancies considered for allogeneic bone marrow transplant from HLA-identical sibling donor, single antigen mismatched related or unrelated donor marrow /peripheral blood stem cell (PBSC) or cord blood available for marrow donation.

    First remission:

    • if remission not achieved by day28
    • high risk cytogenetic features, including t(9;22) or t(4;11) Second or third remission
  2. Signed informed consent.

Exclusion Criteria:

1. Organ criteria:

  1. Cardiac: ECHO shortening fraction <27%
  2. Renal: Creatinine clearance <60 ml/min/1.73 m2
  3. Hepatic: Bilirubin >1.5 mg/dl, transaminases <3x normal
  4. Infection: active viral, fungal or bacterial infection including HIV.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00795886

Locations
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Michael Pulsipher, MD Primary Children's Medical Center
  More Information

No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00795886     History of Changes
Other Study ID Numbers: HCI14044
Study First Received: November 19, 2008
Results First Received: March 1, 2011
Last Updated: July 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
ALL
Cancer
Stem Cell Transplant

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014