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

March 11, 2015 updated by: Children's Hospital of Philadelphia

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • Rapamune
  • rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
within 21 days following administration of sirolimus

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Collaborators

The Leukemia and Lymphoma Society
National Childhood Cancer Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

September 10, 2003

First Submitted That Met QC Criteria

September 10, 2003

First Posted (Estimate)

September 11, 2003

Study Record Updates

Last Update Posted (Estimate)

March 12, 2015

Last Update Submitted That Met QC Criteria

March 11, 2015

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000321392
  • CHP-755
  • CHP-IRB-2002-12-3086

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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