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Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00083070
Enrollment
16
Registered
2004-05-17
Start date
2004-03-31
Completion date
2008-06-30
Last updated
2014-02-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, relapsing chronic myelogenous leukemia, childhood acute promyelocytic leukemia (M3), blastic phase chronic myelogenous leukemia

Brief 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.

Detailed 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.

Interventions

DRUGtemozolomide

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Children's Oncology Group
Lead SponsorNETWORK

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frame
Toxicity as assessed by CTCAE 3.0
Pharmacokinetics as assessed by CI, area under the curve (AUC), and half-life (T ½)
Maximum tolerated dose and recommended phase II dose

Secondary

MeasureTime frame
Antitumor activity
Biologic activity and mechanisms of resistance

Countries

Canada, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026