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

This study has suspended participant recruitment.
(Recruiting/enrolling participants halted prematurely but potentially will resume)
Sponsor:
Collaborators:
National Childhood Cancer Foundation
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00068302
First received: September 10, 2003
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Drug: sirolimus
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Subjects will be assessed for toxicity on days 3, 7 and 21


Secondary Outcome Measures:
  • Response as assessed by radiologic scans after each course of treatment [ Time Frame: day 21 ] [ Designated as safety issue: No ]
    Response will be assessed on day 21 of cycle 1


Enrollment: 10
Study Start Date: January 2003
Estimated Study Completion Date: July 2013
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068302

Locations
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
Investigators
Study Chair: Susan Rheingold, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00068302     History of Changes
Other Study ID Numbers: CDR0000321392, CHP-755, CHP-IRB-2002-12-3086
Study First Received: September 10, 2003
Last Updated: July 1, 2013
Health Authority: United States: Institutional Review Board

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:
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014