Trial of Sirolimus and Methotrexate in Relapsed/Refractory Lymphoblastic Leukemia and Lymphoma
Condition: Cancer; Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Sirolimus and Methotrexate
Intervention description: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
Intervention MeSH terms: Sirolimus; Methotrexate; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Maximum age: 25 Years
Healthy volunteers: No
Keywords: Leukemia; Non-Hodgkin's Lymphoma

Summary:

      This is a phase 2 study looking at efficacy and toxicity of oral sirolimus in combination
      with oral methotrexate in children with refractory/relapsed ALL or NHL.

      Secondary objectives include characterizing the trough levels produced by administration of
      oral sirolimus in children with refractory/relapsed ALL/NHL and to evaluate the effect of
      sirolimus on intracellular targets related to mTOR inhibition.
    

Eligibility criteria:

        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.