sirolimus in treating young patients with relapsed or refractory acute leukemia or non-hodgkin's lymphoma

Conditions: Leukemia; Lymphoma

Summary: rationale: drugs used in chemotherapy such as sirolimus use different ways to stop cancer cells from dividing so they stop growing or die. purpose: this phase i trial is studying the side effects and best dose of sirolimus in treating young patients with relapsed or refractory acute leukemia or non-hodgkin's lymphoma.

objectives: * determine the maximum tolerated dose of sirolimus in pediatric patients with refractory or relapsed acute leukemia or non-hodgkin's lymphoma. * determine the dose-limiting toxic effects of this drug in these patients. * determine the trough levels produced by this drug in these patients. * determine the anti-leukemia/lymphoma activity of this drug in these patients. outline: this is an open-label, dose-escalation study. patients receive oral sirolimus once daily on days 1-21. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed for survival. projected accrual: a total of 3-30 patients will be accrued for this study within 2 years.

Eligibility criteria:
disease characteristics: * histologically confirmed diagnosis of 1 of the following: * acute lymphoblastic leukemia (all) or acute myeloid leukemia (aml) * at least 25% blasts in the bone marrow * recurrent or refractory disease * non-hodgkin's lymphoma (nhl) * second or greater relapse as determined by physical or radiological evidence * disease for which there is no known curative therapy patient characteristics: age * 21 and under performance status * karnofsky 50-100% (patients over 10 years of age) * lansky 50-100% (patients 10 years of age and under) life expectancy * at least 4 weeks hematopoietic * absolute neutrophil count at least 1,000/mm\^3\* * platelet count at least 75,000/mm\^3 (transfusion independent)\* * hemoglobin at least 8.0 g/dl (may receive red blood cells (rbc) transfusions)\* note: \*patients with all, aml, and nhl with tumor metastatic to bone marrow, with granulocytopenia, anemia, and/or thrombocytopenia are eligible, but will not be evaluable for hematological toxicity hepatic * bilirubin no greater than 1.5 times normal * alanine aminotransferase (alt) no greater than 5 times normal * albumin at least 2 g/dl renal * creatinine based on age, as follows: * no greater than 0.8 mg/dl (5 years of age and under) * no greater than 1.0 mg/dl (6 to 10 years of age) * no greater than 1.2 mg/dl (11 to 15 years of age) * no greater than 1.5 mg/dl (over 15 years of age) or * creatinine clearance or radioisotope glomerular filtration rate at least 70 ml/min cardiovascular * shortening fraction at least 28% by echocardiogram or * ejection fraction at least 50% by gated radionuclide other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * able to ingest oral medication * no known allergy to sirolimus, tacrolimus, or other mammalian target of rapamycin (mtor) inhibitors * no uncontrolled active infection * fungal disease must be stable for at least 2 weeks prior to study entry * documented negative blood cultures prior to study entry for patients with bacteremia * no active graft-versus-host disease prior concurrent therapy: biologic therapy * recovered from prior immunotherapy * more than 1 week since prior hematopoietic growth factors except for epoetin alfa * at least 7 days since prior biologic antineoplastic agents * at least 3 months since prior bone marrow or stem cell transplantation chemotherapy * recovered from all prior chemotherapy * more than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) * prior hydroxyurea within the past 2 weeks is allowed provided peripheral blast count has been stable or rising for at least 3 days endocrine therapy * prior corticosteroids within the past 2 weeks are allowed provided peripheral blast count has been stable or rising for at least 3 days radiotherapy * recovered from prior radiotherapy * at least 2 weeks since prior local palliative radiotherapy * at least 4 weeks since prior craniospinal radiotherapy or radiation to the pelvis of 50% or more * at least 4 weeks since prior substantial bone marrow radiotherapy * no concurrent radiotherapy, except for emergent situations or persistent extramedullary disease with resolution of bone marrow disease surgery * not specified other * no other concurrent investigational antineoplastic drugs * no concurrent administration of any of the following: * ketoconazole * tacrolimus * cyclosporine * rifampin * diltiazem

Keywords: recurrent childhood lymphoblastic lymphoma recurrent childhood small noncleaved cell lymphoma recurrent childhood large cell lymphoma recurrent childhood acute myeloid leukemia recurrent childhood acute lymphoblastic leukemia