Trial of Sirolimus and Methotrexate in Relapsed/Refractory Lymphoblastic Leukemia and Lymphoma

Inclusion Criteria:

• Patients </= 25 years of age, at time of enrollment, with second or greater relapse of ALL or NHL. For ALL must have histologic diagnosis with >10% blasts in the marrow and for lymphoblastic lymphoma or peripheral T-cell lymphoma must have radiologic or physical evidence of recurrence.
• Lansky > 50% or Karnofsky > 50%
• Negative Pregnancy Test
• Creatinine clearance or radioisotope GFR > 70ml/min/m2 OR serum creatinine based on age /gender
• Pulse ox >94%
• Total Bilirubin <1.5 x normal for age
• ALT < 5 x normal for age
• Albumin > 2g/dL
• Shortening fraction by echo > 28% OR ejection fraction > 50% by gated radionuclide study

Exclusion Criteria:

• Patient has known allergies to sirolimus,FK-506 or mTOR inhibitors
• Patient is taking other investigational anti-neoplastic drugs
• Patient received no myelosuppressive chemo within 14 days
• < 14 days have elapsed since local palliative XRT (small port) < 28 days since prior craniospinal XRT or 50% radiation of pelvis <28 days if other substantial BM radiation
• Hematopoietic growth factors within 7 days of entry (except erythropoietin.)
• Patient has taken any biologic agents within 14 days
• Post BMT/SCT - evidence of active GVHD, at least > 3 months must have elapsed
• Patient has uncontrolled infection (if patients with fungal disease, stable for < 14 days and patients with bacteremia without negative blood culture
• Existing non-hematologic toxicities > grade 2

Use of steroids or hydroxyurea is permitted upto 14 days prior to entry.