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

Phase 1
1 Year
21 Years
Not Enrolling

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Trial Information

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



- 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.


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

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

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

Inclusion Criteria


- 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



- 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


- 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)


- ALT ≤ 5 times upper limit of normal (ULN)

- Albumin ≥ 2 g/dL

- Bilirubin ≤ 1.5 times ULN


- Creatinine normal for age OR

- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min/1.73 m^2


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection


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


- 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

- 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


- Recovered from prior radiotherapy

- No concurrent radiotherapy


- Not specified


- No other concurrent anticancer agents

- No other concurrent investigational drugs

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and recommended phase II dose

Safety Issue:


Principal Investigator

Terzah M. Horton, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Texas Children's Cancer Center


United States: Federal Government

Study ID:




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



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