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

NCT00068302 | Terminated Phase 1 DMC

• 3 other identifiers: CDR0000321392CHP-755CHP-IRB-2002-12-3086
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia; Lymphoma

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

Outcome Measures

Primary Outcomes (1)

• Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment

  Subjects will be assessed for toxicity on days 3, 7 and 21

  within 21 days following administration of sirolimus

Secondary Outcomes (1)

• Response as assessed by radiologic scans after each course of treatment

  day 21

Study Arms (1)

Sirolimus

EXPERIMENTAL

This is a dose escalation study including 4-dose levels. Subjects will receive a one-time loading dose of sirolimus on day 0, time 0. Subsequent dosing at the assigned dose level will start 24 hours following the initial loading dose

Drug: sirolimus

Interventions

sirolimus DRUG

3-6 subjects will be enrolled into each dose level

Also known as: rapamycin, Rapamune

Sirolimus

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Childhood Cancer Foundation: collaborator
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Burkitt Lymphoma; Dendritic Cell Sarcoma, Interdigitating; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Histiocytic Disorders, Malignant; Histiocytosis; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Susan Rheingold, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2003
• First Posted: September 11, 2003
• Study Start: January 1, 2003
• Primary Completion: April 1, 2009
• Study Completion: July 1, 2013
• Last Updated: March 12, 2015

Record last verified: 2013-07

Locations

US (1)