Patient case: 1-year-old male with acute myeloid leukemia; genetic feature: IDH1

Clinical trial: Temozolomide in Treating Young Patients With Refractory or Recurrent Leukemia

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.

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

Relevance to patient case: not relevant