Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

Leukemia Clinical Trial

Official title:

A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00083070
• Other study ID #: ADVL0411
• Secondary ID: CDR0000362059COG
• Status: Completed
• Phase: Phase 1
• First received: May 14, 2004
• Last updated: February 18, 2014
• Start date: March 2004
• Est. completion date: June 2008

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in 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 temozolomide in treating young patients with refractory or recurrent leukemia.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and recommended phase II dose of temozolomide in pediatric patients with refractory or recurrent leukemia.

• Determine the toxic effects of this drug in these patients.

• Determine the pharmacokinetics of this drug in these patients.

Secondary

• Determine the antitumor activity of this drug in these patients.

• Determine the biologic activity and mechanism(s) of resistance to this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18-24 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2008
• Est. primary completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed leukemia of any of the following types:

• Acute lymphoblastic leukemia

• Acute myeloid leukemia

• Chronic myelogenous leukemia in blast crisis

• Refractory or recurrent disease

• Immunophenotypic confirmation of disease at initial diagnosis or recurrence

• More than 25% blasts in the bone marrow (M3)

• Active extramedullary disease allowed except for leptomeningeal disease

• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life

• No active CNS disease

PATIENT CHARACTERISTICS:

Age

• 1 to 21

Performance status

• Karnofsky 50-100% (for patients > 10 years of age)

• Lansky 50-100% (for patients = 10 years of age)

Life expectancy

• Not specified

Hematopoietic

• WBC < 30,000/mm^3 (hydroxyurea or leukapheresis allowed at the discretion of the principal investigator)

• Platelet count = 20,000/mm^3 (platelet transfusions allowed)

• Hemoglobin = 8.0 g/dL (red blood cell transfusions allowed)

Hepatic

• ALT = 5 times upper limit of normal (ULN)

• Albumin = 2 g/dL

• Bilirubin = 1.5 times ULN

Renal

• Creatinine normal for age OR

• Creatinine clearance OR radioisotope glomerular filtration rate = 70 mL/min/1.73 m^2

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 7 days since prior biologic therapy, including immunotherapy

• At least 3 months since prior stem cell transplantation

• No evidence of active graft-vs-host disease

• No concurrent biologic therapy

• No concurrent immunotherapy

Chemotherapy

• Recovered from prior chemotherapy

• At least 6 weeks since prior nitrosoureas

• Prior therapy with hydroxyurea allowed for up to 24 hours before initiation of study drug

• No other concurrent chemotherapy

Endocrine therapy

• Concurrent hydrocortisone or other corticosteroids allowed as premedications prior to blood product transfusions in patients with prior severe allergic reactions

Radiotherapy

• Recovered from prior radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent anticancer agents

• No other concurrent investigational drugs

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• temozolomide

Locations

Country	Name	City	State
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Fairview University Medical Center - University Campus	Minneapolis	Minnesota
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

Horton TM, Dolan E, Hegde M, et al.: A phase I study of temozolomide (Temodar®) in pediatric patients with relapsed or refractory leukemia: a Children's Oncology Group study. [Abstract] Blood 106 (11): A-4455, 2005.

Horton TM, Thompson PA, Berg SL, Adamson PC, Ingle AM, Dolan ME, Delaney SM, Hedge M, Weiss HL, Wu MF, Blaney SM; Children's Oncology Group Study. Phase I pharmacokinetic and pharmacodynamic study of temozolomide in pediatric patients with refractory or r — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and recommended phase II dose			Yes
Primary	Toxicity as assessed by CTCAE 3.0			Yes
Primary	Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½)			No
Secondary	Antitumor activity			No
Secondary	Biologic activity and mechanisms of resistance			No