A Trial of Temsirolimus With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma

INCLUSION CRITERIA

-Patients must be greater than or equal to 12 months and ≤ 21 years of age at the time of study enrollment.

Patients must have one of the following:

Leukemia

• Bone marrow involvement defined as ALL ≥ 25% blasts (M2 or M3) with or without extramedullary involvement.
• Refractory bone marrow involvement defined as MRD ≥ 0.1% blasts done at a COG-approved MRD testing lab after most recent treatment regimen. in the bone marrow (M23) and any CNS status. OR
• Newly diagnosed patients (T or B-cell ALL) with refractory bone marrow involvement after Consolidation therapy are eligible.
• First relapse B-cell ALL patients are eligible with refractory disease.
• Second or greater relapse B-cell patients are eligible at time of relapse or with refractory disease.
• First or greater relapse T-cell ALL patients are eligible at time of relapse or with refractory disease.
• Isolated CNS 2 or 3 patients with 16 years of age and Lansky greater than or equal to 50 for patients ≤ 16 years of age.

Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy.

Patients with leukemia or lymphoma who relapse while receiving maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study.

At least 14 days must have elapsed after the completion of cytotoxic therapy, with the exception of hydroxyurea.

Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.

Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair

Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines. or chimeric antigen receptor T cell (CART) therapy or tumor vaccines.

Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of a monoclonal antibody. (ie: Rituximab = 66 days, Epratuzumab = 69 days). Patients must have been off blinatumomab infusion for at least 4 days and all drug-related toxicity must have resolved to grade 2 or lower as outlined in the inclusion and exclusion criteria

XRT: At least 14 days after local palliative XRT (small port); At least 84 days must have elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of pelvis; At least 42 days must have elapsed if other substantial marrow radiation.

Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion.

Adequate Bone Marrow Function Defined as: Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be greater than or equal to 20,000/mm3 to initiate therapy (may receive platelet transfusions). Patients should not be known to be refractory to red blood cell or platelet transfusions.

Adequate Renal Function Defined as:

• Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2 or
• Normal serum creatinine based on age and gender.

Adequate Liver Function Defined as:

• Total bilirubin (sum of conjugated + unconjugated) must be less than or equal to 1.5 x normal per institutional normal values for age.
• SGPT (ALT) and SGOT (AST) must be less than 3 x institutional upper limit of normal (Grade 1 or less per CTCAE 4).

--GGT must be less than 2.5 x institutional upper limit of normal (Grade 1 or less per CTCAE 4).

• Serum albumin greater than or equal to 2 g/dL.
• The hepatic requirements may be waived for patients with elevations clearly due to leukemic infiltration after consultation with the Study Chair or Vice Chair.
• Fasting or non-fasting serum triglycerid