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

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ClinicalTrials.gov 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
Information provided by (Responsible Party):

September 10, 2003
September 11, 2003
March 12, 2015
January 2003
April 2009   (Final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00068302 on ClinicalTrials.gov Archive Site
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
Not Provided
Not Provided
Not Provided
Sirolimus in Treating Young Patients With Relapsed or Refractory Acute Leukemia or Non-Hodgkin's Lymphoma
A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma

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.


  • 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.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
Drug: sirolimus
3-6 subjects will be enrolled into each dose level
Other Names:
  • rapamycin
  • Rapamune
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
Intervention: Drug: sirolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
July 2013
April 2009   (Final data collection date for primary outcome measure)


  • 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
Sexes Eligible for Study: All
up to 21 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
  • National Childhood Cancer Foundation
  • The Leukemia and Lymphoma Society
Study Chair: Susan Rheingold, MD Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP