Phase 2 Trial of Sirolimus and Methotrexate in Relapsed/Refractory Lymphoblastic Leukemia and Lymphoma
At present children who have bone marrow or combined bone marrow and extramedullary relapses
of acute leukemia while on therapy have 5-20% of long-term survival. Newer, targeted agents
need to be identified and integrated into the present cytotoxic chemotherapy regimens.
Biologically targeted cancer agents, including signal transduction inhibitors like mammalian
target of rapamycin inhibitors (MTIs), have shown great promise in treating hematologic
malignancies. A Phase 1 trial of sirolimus (an MTI) alone performed at CHOP has been well
tolerated with no DLTs and has evidence of hitting the biologic target. While signal
transduction inhibitors may be efficacious as single agents, it is more likely that these
targeted agents will demonstrate greater efficacy in combination with other cytotoxic
agents.Based upon pre-clinical humanized ALL mouse models we propose to study the toxicity
and efficacy of adding sirolimus to oral methotrexate in relapsed and refractory patients.
Patients < 25 years of age, at time of enrollment, with second or greater relapse of ALL or
NHL (lymphoblastic lymphoma or peripheral T-cell lymphoma) are eligible. ALL patients must
have at least 10% blasts in their marrow and NHL patients must have radiologic or physical
evidence of recurrence.
Patients will be started on daily oral sirolimus that is dosed based upon goal trough levels
and weekly oral methotrexate. All therapy can be done as an outpatient.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy and toxicity of oral sirolimus when given with oral methotrexate
Determine the efficacy of oral sirolimus when given in combination with methotrexate in children with refractory/relapsed ALL or NHL.
Disease status will be assessed every 28 days, toxicity will be assessed continually.
Susan R. Rheingold, MD
Children's Hospital of Philadelphia
United States: Institutional Review Board
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