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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00068302
Recruitment Status : Terminated (Recruiting/enrolling participants halted prematurely but potentially will resume)
First Posted : September 11, 2003
Last Update Posted : March 12, 2015
National Childhood Cancer Foundation
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Drug: sirolimus Phase 1

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma
Study Start Date : January 2003
Actual Primary Completion Date : April 2009
Actual Study Completion Date : July 2013

Arm Intervention/treatment
Experimental: Sirolimus
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
3-6 subjects will be enrolled into each dose level
Other Names:
  • rapamycin
  • Rapamune

Primary Outcome Measures :
  1. Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment [ Time Frame: within 21 days following administration of sirolimus ]
    Subjects will be assessed for toxicity on days 3, 7 and 21

Secondary Outcome Measures :
  1. Response as assessed by radiologic scans after each course of treatment [ Time Frame: day 21 ]
    Response will be assessed on day 21 of cycle 1

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 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


  • 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


  • Bilirubin no greater than 1.5 times normal
  • alanine aminotransferase (ALT) no greater than 5 times normal
  • Albumin at least 2 g/dL


  • 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


  • Shortening fraction at least 28% by echocardiogram OR
  • Ejection fraction at least 50% by gated radionuclide


  • 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


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


  • 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


  • 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


  • Not specified


  • No other concurrent investigational antineoplastic drugs
  • No concurrent administration of any of the following:

    • Ketoconazole
    • Tacrolimus
    • Cyclosporine
    • Rifampin
    • Diltiazem

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00068302

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United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Childhood Cancer Foundation
The Leukemia and Lymphoma Society
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Study Chair: Susan Rheingold, MD Children's Hospital of Philadelphia

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Responsible Party: Children's Hospital of Philadelphia Identifier: NCT00068302     History of Changes
Other Study ID Numbers: CDR0000321392
First Posted: September 11, 2003    Key Record Dates
Last Update Posted: March 12, 2015
Last Verified: July 2013
Keywords provided by Children's Hospital of Philadelphia:
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
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs