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

• Status: Completed
• Trial end date: 2017-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborator: The Leukemia and Lymphoma Society
• Treatments: Everolimus; Methotrexate; Sirolimus

Criteria

Inclusion Criteria:

• PatientsALL 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.