Clinical trial · Interventional
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
NCT01162551CI-TRIAL-00039900completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Cancer | Malignant Neoplasm | ALIAS | 0.90 |
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
| Lymphoma | Lymphoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Sirolimus and Methotrexate | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Sirolimus and Methotrexate
- description
- 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
- interventionNames
- Drug: Sirolimus and Methotrexate
Primary outcomes (1)
- measure
- Response Rate
- timeFrame
- Day 28
- description
- Number of participants who achieve a Complete Response (CR), Complete Response with in the absence of total platelet recovery (CRp), or Partial Response (PR). Per response criteria in this protocol: Complete Response (CR) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease and recovery of peripheral blood counts (absolute neutrophil count (ANC)\> 500/μL and platelets \> 50,000/ μL); Complete Response in the absence of total platelet recovery (CRp) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease with recovery of peripheral blood counts except for platelets (ANC\> 500/μL, platelets \< 50,000uL); and Partial Response (PR) - M2 bone marrow (5% but \<25% blasts), with no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts (ANC \> 500/μL and platelets \>50,000/μL).
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 25 Years
Show eligibility criteria text
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.
References
Publications (8)
- BACKGROUNDTeachey DT, Sheen C, Hall J, Ryan T, Brown VI, Fish J, Reid GS, Seif AE, Norris R, Chang YJ, Carroll M, Grupp SA. mTOR inhibitors are synergistic with methotrexate: an effective combination to treat acute lymphoblastic leukemia. Blood. 2008 Sep 1;112(5):2020-3. doi: 10.1182/blood-2008-02-137141. Epub 2008 Jun 10. PMID 18544682
- BACKGROUNDHoughton PJ, Morton CL, Kolb EA, Gorlick R, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Apr;50(4):799-805. doi: 10.1002/pbc.21296. PMID 17635004
- BACKGROUNDTeachey DT, Obzut DA, Cooperman J, Fang J, Carroll M, Choi JK, Houghton PJ, Brown VI, Grupp SA. The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL. Blood. 2006 Feb 1;107(3):1149-55. doi: 10.1182/blood-2005-05-1935. Epub 2005 Sep 29. PMID 16195324
- BACKGROUNDBrown VI, Fang J, Alcorn K, Barr R, Kim JM, Wasserman R, Grupp SA. Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15113-8. doi: 10.1073/pnas.2436348100. Epub 2003 Dec 1. PMID 14657335
- BACKGROUNDLuger S, Perl A, Kemner A. A phase I dose escalation study of the mTOR inhibitor sirolimus and MEC chemotherapy targeting signal transduction in leukemic stem cells for acute myeloid leukemia. . Blood. 2006;106:161.
- BACKGROUNDMorrison DJ, Hogan LE, Condos G, Bhatla T, Germino N, Moskowitz NP, Lee L, Bhojwani D, Horton TM, Belitskaya-Levy I, Greenberger LM, Horak ID, Grupp SA, Teachey DT, Raetz EA, Carroll WL. Endogenous knockdown of survivin improves chemotherapeutic response in ALL models. Leukemia. 2012 Feb;26(2):271-9. doi: 10.1038/leu.2011.199. Epub 2011 Aug 16. PMID 21844871
- Sheen C, Vincent T, Barrett D, Horwitz EM, Hulitt J, Strong E, Grupp SA, Teachey DT. Statins are active in acute lymphoblastic leukaemia (ALL): a therapy that may treat ALL and prevent avascular necrosis. Br J Haematol. 2011 Nov;155(3):403-7. doi: 10.1111/j.1365-2141.2011.08696.x. Epub 2011 May 9. No abstract available.