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Graft Versus Host Disease

Sirolimus-Based Graft Versus Host Disease Prophylaxis Post Transplant (COG ASCT0431)
A Randomized Trial Of Sirolimus-Based Graft Versus Host Disease Prophylaxis After Hematopoietic Stem Cell Transplant
Status Conditions Phase Study ID
Closed Graft Versus Host Disease
Leukemia
Phase III COG ASCT0431
NCT00382109
Summary

RATIONALE: Giving chemotherapy, such as thiotepa and cyclophosphamide, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, and sirolimus after the transplant may stop this from happening. It is not yet known whether tacrolimus and methotrexate are more effective with or without sirolimus in preventing graft-versus-host disease.

PURPOSE: This randomized phase III trial is studying tacrolimus, methotrexate, and sirolimus to see how well they work compared to tacrolimus and methotrexate in preventing graft-versus-host disease in young patients who are undergoing donor stem cell transplant for intermediate-risk or high-risk acute lymphoblastic leukemia in second complete remission.


Investigator
Jean Sanders, MD
Location    
Seattle Cancer Care Alliance 800-804-8824  
Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed acute lymphoblastic leukemia (ALL)* in second complete remission (CR2) (M1 bone marrow, < 5% blasts by morphology) meeting the following criteria:

    • Eligible for matched sibling transplantation AND intermediate-risk disease meeting 1 of the following criteria:

      • B-lineage ALL in CR2 after a late first bone marrow (BM) relapse (≥ 36 months after the initiation of primary chemotherapy) with or without associated extramedullary disease
      • B-lineage ALL in CR2 after a very early isolated extramedullary relapse**
    • Eligible for other related donor, unrelated donor, or matched sibling transplantation AND high-risk disease meeting 1 of the following criteria:

      • In CR2 after an early first BM relapse (< 36 months from initiation of primary chemotherapy)
      • T-lineage ALL in CR2 after a first BM relapse occurring at any time after initiation of primary chemotherapy
      • Philadelphia chromosome-positive ALL in CR2 after a first BM relapse occurring at any time after the initiation of primary chemotherapy
      • T-lineage ALL in CR2 after a very early isolated extramedullary relapse** NOTE: *ALL defined as bone marrow with > 25% L1 or L2 lymphoblasts (i.e., M3 marrow). Patients with > 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are considered to have Burkitt's lymphoma or mature B-cell leukemia and are not eligible.

NOTE: **Less than 18 months after initiation of primary chemotherapy

  • Enrolled on an appropriate COG relapsed ALL clinical trial meeting 1 of the following criteria:

    • Must proceed directly to transplantation after completing the required study therapy (i.e., 1 induction course and 2 consolidation courses)
    • Patients not on a COG relapsed ALL clinical trial are eligible provided they have received ≥ 1 round of re-induction lasting 4-6 weeks and 1 round of intensive consolidation chemotherapy lasting 3-6 weeks
  • No B-cell ALL L3 morphology with evidence of myc translocation by molecular or cytogenetic technique
  • No Down syndrome
  • No evidence of active CNS or other extramedullary disease (i.e., no CNS2)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lansky PS 60-100% (for patients ≤ 16 years of age)
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
  • ALT or AST < 5 times upper limit of normal
  • Bilirubin < 2.5 mg/dL (unless an increase is attributable to Gilbert's syndrome)
  • Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
  • FEV_1 ≥ 60% by pulmonary function tests (PFTs)
  • FVC ≥ 60% by PFTs
  • DLCO ≥ 60% by PFTs
  • For children who are unable to cooperate for PFTs all of the following criteria must be met:

    • No evidence of dyspnea at rest
    • No exercise intolerance
    • No requirement for supplemental oxygen therapy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV or uncontrolled fungal, bacterial, or viral infection

    • Fungal infection acquired during induction therapy allowed provided there is a significant response to antifungal therapy with minimal or no evidence of disease by CT scan

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic or autologous stem cell transplantation
  • No prior or concurrent voriconazole unless prior voriconazole therapy is completed or a different agent is substituted for voriconazole prior to study entry
  • No concurrent grapefruit juice during sirolimus administration
  • Other concurrent immunosuppressants allowed
Last Updated
July 07, 2011
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.