A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias
1 Year
21 Years
Both
Leukemia
Trial Information
A Phase I Trial Of Temozolomide In Pediatric Patients With Refractory/Recurrent Leukemias
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose and recommended phase II dose
Safety Issue:
Yes
Principal Investigator
Terzah M. Horton, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Texas Children's Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000362059
NCT ID:
NCT00083070
Start Date:
March 2004
Completion Date:
Related Keywords:
- Leukemia
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood acute myeloid leukemia
- relapsing chronic myelogenous leukemia
- childhood acute promyelocytic leukemia (M3)
- blastic phase chronic myelogenous leukemia
- Leukemia
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
| Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Herbert Irving Comprehensive Cancer Center at Columbia University | New York, New York 10032 |
| Fairview University Medical Center - University Campus | Minneapolis, Minnesota 55455 |
| Stanford Cancer Center at Stanford University Medical Center | Stanford, California 94305 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
