NCT01162551

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

Phase 2 Trial of Sirolimus and Methotrexate in Relapsed/Refractory Lymphoblastic Leukemia and Lymphoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 25 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Cancer
• Leukemia
• Lymphoma

Interventions

Type	Name	Description
DRUG	Sirolimus and Methotrexate	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.

Timeline

• Start date: 2010-05-01
• Primary completion: 2017-02-01
• Completion: 2017-02-01
• First posted: 2010-07-14
• Last updated: 2019-08-06
• Results posted: 2019-08-06

Locations

1 site across 1 country: United States