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

Roswell Park Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Leukemia

Treatments: Drug: cytarabine; Drug: irinotecan hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00053144

P30CA016056 (U.S. NIH Grant/Contract)

RPCI-RPC-9901

CDR0000269286

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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