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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: cytarabine

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Maria R. Baer, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): February 1, 2003
• Study Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: January 27, 2003
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Estimate): March 8, 2011
• Last Update Submitted That Met QC Criteria: March 7, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: secondary acute myeloid leukemia; recurrent adult acute myeloid leukemia; adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; adult acute promyelocytic leukemia (M3)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Cytarabine
• Other Study ID Numbers: CDR0000269286; P30CA016056 (U.S. NIH Grant/Contract); RPCI-RPC-9901