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

Clinical trial: Irinotecan and Cytarabine in Treating Patients With Refractory or Recurrent Acute Myeloid Leukemia or Chronic Myelogenous Leukemia

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
  PURPOSE: Phase I trial to study the effectiveness of combining irinotecan with cytarabine in treating patients who have refractory or recurrent acute myeloid leukemia or chronic myelogenous leukemia.

Detailed description: OBJECTIVES:
  -  Determine the activity of irinotecan and cytarabine in patients with refractory or recurrent acute myeloid leukemia or chronic myelogenous leukemia in myeloid blast transformation.
  -  Determine the pharmacokinetics of this regimen in these patients.
  -  Determine the maximum tolerated dose of irinotecan in this regimen in these patients.
  -  Correlate the clinical activity of this drug with cellular endpoints associated with DNA synthesis inhibition, DNA repair, induction of apoptosis, and drug resistance in these patients.
  OUTLINE: This is a dose-escalation study of irinotecan.
  Patients receive irinotecan IV over 90 minutes and cytarabine IV over 60 minutes on days 1-6. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. An additional 9 patients with refractory/relapsed acute myeloid leukemia and 9 patients with chronic myelogenous leukemia in myeloid blast transformation are treated at the MTD.
  Patients are followed for survival.
  PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 2.5 years.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed acute myeloid leukemia (M0-M7)
  -  De novo or secondary disease
  -  Previously treated and refractory to prior therapy (which has included high-dose cytarabine and an anthracycline)
  -  Antecedent hematologic disorders allowed OR
  -  Histologically confirmed Philadelphia chromosome-positive chronic myelogenous leukemia in myeloid blast transformation
  -  Treated or untreated
  -  Blast transformation defined by at least 20% blasts in marrow and/or blood
  -  Myeloid lineage defined by immunophenotyping
  PATIENT CHARACTERISTICS:
  Age
  -  15 and over
  Performance status
  -  0-3
  Life expectancy
  -  At least 4 weeks
  Hematopoietic
  -  See Disease Characteristics
  Hepatic
  -  Bilirubin less than 2 times upper limit of normal (ULN)
  -  SGOT less than 2 times ULN
  Renal
  -  Creatinine less than 1.5 times ULN
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  No other concurrent serious medical or psychiatric illness that would preclude study consent
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  Not specified
  Chemotherapy
  -  See Disease Characteristics
  -  Prior chemotherapy for an antecedent malignancy or other medical condition allowed
  Endocrine therapy
  -  Not specified
  Radiotherapy
  -  Prior radiotherapy for an antecedent malignancy or other medical condition allowed
  Surgery
  -  Not specified

Relevance to patient case: not relevant