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

NCT ID: NCT00068302

Last Updated: 2015-03-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2013-07-31

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.

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.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

sirolimus

Intervention Type: DRUG

3-6 subjects will be enrolled into each dose level

Interventions

sirolimus

3-6 subjects will be enrolled into each dose level

Intervention Type: DRUG

Other Intervention Names

rapamycin; Rapamune

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Childhood Cancer Foundation

UNKNOWN

Sponsor Role: collaborator

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Rheingold, MD

Role: STUDY_CHAIR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

CHP-755

Identifier Type: -

Identifier Source: secondary_id

CHP-IRB-2002-12-3086

Identifier Type: -

Identifier Source: secondary_id

CDR0000321392

Identifier Type: -

Identifier Source: org_study_id