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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Hospital
  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 July 22, 2014