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

Lymphoma Clinical Trial

Official title:

A Phase I Trial Of Sirolimus In Relapsed/Refractory Leukemia And Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00068302
• Other study ID #: CDR0000321392
• Secondary ID: CHP-755CHP-IRB-2
• Status: Terminated
• Phase: Phase 1
• First received: September 10, 2003
• Last updated: March 11, 2015
• Start date: January 2003
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: July 2013
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• sirolimus
3-6 subjects will be enrolled into each dose level

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Childhood Cancer Foundation, The Leukemia and Lymphoma Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity as assessed by Common Toxicity Criteria (CTC) toxicity criteria after the first course of treatment	Subjects will be assessed for toxicity on days 3, 7 and 21	within 21 days following administration of sirolimus	Yes
Secondary	Response as assessed by radiologic scans after each course of treatment	Response will be assessed on day 21 of cycle 1	day 21	No