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

Completed · Phase 1

Conditions studied: Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Lymphoma, Peripheral T-cell Lymphoma

In brief

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).

Key facts

Study ID

NCT01614197

Run by

Therapeutic Advances in Childhood Leukemia Consortium

People needed

16

Starts

2015-07-03

Expected to finish

2020-09-04

Last updated by the study team

2023-07-27

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 < 0.1% MRD bone marrow involvement are not eligible.
• Lymphoma
• Patient must have relapsed or refractory lymphoblastic lymphoma or peripheral T-cell lymphoma.
• Patient must have histologic verification of disease at original diagnosis.
• Patient must have evaluable or measurable disease documented by clinical or radiographic criteria or bone marrow disease present at study entry.
• Patients may have CNS 2 or 3 disease
• 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 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.

You may not qualify if…

• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
• Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. The definition of "investigational" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia)
• Anti-cancer Agents: Patients who are currently receiving or may receive while on therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible [except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]. Intrathecal chemotherapy (at the discretion of the primary oncologist) may be given up to one week prior to the initiation of study therapy.
• Anti-GVHD or agents to prevent organ rejection post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial. At least 3 half-lives must have elapsed after the last dose of GVHD meds.
• Anticoagulants: Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible. At least 3 half-lives must have elapsed after the last dose of anticoagulants.
• Angiotensin-converting enzyme (ACE) inhibitors: Patients who are currently receiving ACE inhibitors are not eligible due to the development of angioneurotic edema-type reactions in some subjects who received concurrent treatment with temsirolimus + ACE inhibitors. At least 3 half-lives must have elapsed after the last dose of ACE inhibitors.
• Calcium Channel Blockers: Patients who are currently receiving Calcium Channel Blockers are not eligible due to the development of angioneurotic edema-type reactions in some subjects who received concurrent treatment with temsirolimus + Calcium Channel Blockers. At least 3 half-lives must have elapsed after the last dose of Calcium Channel Blockers.
• Enzyme inducing Anti-convulsants: Patients who are currently receiving enzyme inducing anticonvulsants (ie phenytoin, phenobarbitol, or carbamazepine) are not eligible. Stabilizing on a non-hepatic inducing metabolizing anti-convulsant (ie: gabapentin or levetiracetam) prior to study entry is acceptable. At least 3 half-lives must have elapsed after the last dose of enzyme inducing anti-coagulants.
• 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.
• Patient with Burkiett's leukemia and /or lymphoma are not eligible.
• Infection Criteria
• Patients are excluded if they have:
• Positive blood culture within 48 hours of study enrollment;
• Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
• A positive fungal culture within 30 days.
• 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.

Where it is running

• Childrens Hospital Los Angeles — Los Angeles, California, United States
• Children's Hospital Orange County — Orange, California, United States
• UCSF School of Medicine — San Francisco, California, United States
• The Children's Hospital, University of Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• University of Miami Cancer Center — Miami, Florida, United States
• Children's Healthcare of Atlanta, Emory University — Atlanta, Georgia, United States
• Lurie Children's Hospital — Chicago, Illinois, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Dana Farber — Boston, Massachusetts, United States
• C.S. Mott Children's Hospital — Ann Arbor, Michigan, United States
• Childrens Hospital & Clinics of Minnesota — Minneapolis, Minnesota, United States
• Children's Hospital New York-Presbyterian — New York, New York, United States
• Levine Children's Hospital at Carolinas Medical Center — Charlotte, North Carolina, United States
• Rainbow Babies — Cleveland, Ohio, United States
• Nationwide Childrens Hospital — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• St. Jude — Memphis, Tennessee, United States
• University of Texas at Southwestern — Dallas, Texas, United States
• Cook Children's Medical Center — Fort Worth, Texas, United States
• Texas Children's Hospital — Houston, Texas, United States
• Primary Children's — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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