Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

Children's Oncology Group

Status and phase

Completed

Phase 1

Conditions

Leukemia

Treatments

Drug: temozolomide

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00083070

COG-ADVL0411 (Other Identifier)

CDR0000362059 (Other Identifier)

ADVL0411

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

1 to 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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