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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Irinotecan And Cytarabine In Refractory or Relapsed Acute Myeloid Leukemia And In Chronic Myelogenous Leukemia In Myeloid Blast Transformation: Efficacy And In Vitro Correlates

Conditions
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Leukemia

Intervention / Treatment
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* Drug: cytarabine
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cytarabine|nan|
|Drug: irinotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, Philadelphia chromosome positive chronic myelogenous leukemia, secondary acute myeloid leukemia, blastic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, adult acute monocytic leukemia (M5b), adult acute erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute promyelocytic leukemia (M3)