This is a phase I study of temsirolimus (Torisel) combined with dexamethasone, cyclophosphamide and etoposide in patients with relapsed acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL) or peripheral T-cell lymphoma (PTL).
A Phase I Trial of Temsirolimus (CCI-779, Pfizer, Inc.) in Combination With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma
Studies have shown that mTOR inhibitors (MTI) inhibit growth of pre-B and T-cell ALL cell lines in vitro and in ALL xenograft models. The MTI temsirolimus was chosen for use in this study due to its weekly intravenous dosing, its more predictable blood levels, and availability of a single-agent pediatric MTD and its sustained biologic effect due to conversion to sirolimus. This study will determine the maximum tolerated dose of temsirolimus that can given in combination with dexamethasone, cyclophosphamide and etoposide in relapsed ALL, LL or PTL. A standard 3-patient cohort dose-escalation design will be used. Response to treatment will be evaluated. Biology tests will be done to evaluate minimal residual disease (MRD), temsirolimus' effect on glucocorticoid resistance, and mTOR inhibition.
Lymphoblastic Leukemia, Acute, Childhood Lymphoblastic Lymphoma Peripheral T-cell Lymphoma Relapse Lymphoblastic Leukemia Refractory Temsirolimus Acute Childhood Pediatric ALL NHL LL PTL Methotrexate Cytarabine Etoposide Cyclophosphamide Everolimus Sirolimus Etoposide phosphate Hydrocortisone 17-butyrate 21-propionate Cortisol succinate Hydrocortisone acetate Hydrocortisone
Open to people ages 1 year to 21 years
-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:
Refractory disease defined as no more than 1 prior failed salvage attempt following the current relapse, or no more than 2 additional treatment cycles after initial induction failure in newly diagnosed patients.
Patients may have CNS 2 or 3 disease, if other sites of involvement.
Karnofsky greater than or equal to 50% for patients> 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 must have had 2 or more prior therapeutic attempts defined as:
Patients with lymphoma may have refractory disease after first or greater relapse and a single re-induction attempt.
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 42 days after the completion of any type of immunotherapy, e.g.tumor vaccines. or chimeric antigen receptor T cell (CART) therapy.
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 7 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.
Study specific limitations on prior therapy: Patient may not have received therapy with an mTOR inhibitor.
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:
Adequate Liver Function Defined as:
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).
Adequate Cardiac Function Defined As:
Adequate Pulmonary Function Defined as:
Baseline chest x-ray with no evidence of active infectious disease or pneumonitis.
Patients receiving treatment with azoles such as fluconazole or voriconazole which are potent inhibitors of temsirolimus metabolism. At least 3 half-lives must have elapsed after the last dose of azoles.
Patients are excluded if they have:
Active fungal, viral, bacterial, or protozoal infection requiring IV treatment.Chronic prophylaxis therapy to prevent infections is allowed.
Patients with Down syndrome and Fanconi Anemia are excluded.
Patients will be excluded if they have significant concurrent disease, illness,psychiatric disorder or social issue that would compromise patient safety or compliance with protocol treatment or required observations, interfere with consent, study participation, follow up, or interpretation of study results.
Patients with known optic nerve and/or retinal involvement (because it may not be possible to safely delay irradiation) are not eligible. Patients presenting with visual disturbances by history or physical exam should have an ophthalmological exam and, if indicated, an MRI to determine optic nerve or retinal involvement.
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT01614197.
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