Sirolimus in Treating Young Patients With Relapsed or Refractory Acute Leukemia or Non-Hodgkin's Lymphoma

• Status: Terminated
• Trial end date: 2013-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Childhood Cancer Foundation; The Leukemia and Lymphoma Society
• Treatments: Everolimus; Sirolimus

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