STI571 Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia

A Phase I/II Trial of STI571 and High-Dose Cytarabine in Myeloid Blast Crisis of Chronic Myeloid Leukemia

Phase I/II trial to study the effectiveness of combining STI571 and chemotherapy in treating patients who have chronic myelogenous leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells

Study Overview

• Status: Completed
• Conditions: Relapsing Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Phase Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: cytarabine; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of high-dose cytarabine when combined with imatinib mesylate in patients with blastic phase chronic myelogenous leukemia.

II. Determine the safety of this regimen in these patients. III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine the frequency of hematologic and cytogenetic responses, duration of response, and survival of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of cytarabine.

Phase I: Patients who have not previously received imatinib mesylate receive oral imatinib mesylate daily on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive cytarabine IV over 2 hours every 12 hours on days 29-32. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Additional patients are treated at the dose level preceding the MTD. Patients are followed monthly.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles (UCLA )

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of chronic myelogenous leukemia in myeloid blast crisis

  • At least 30% blasts in bone marrow
• Philadelphia chromosome positive by cytogenetic analysis
• bcr/abl translocation by fluorescent in situ hybridization
• Ineligible for or refused allogeneic stem cell transplantation
• Not previously treated with imatinib mesylate OR currently receiving imatinib mesylate with stable disease on 2 bone marrow biopsies at least 2 weeks apart
• Performance status - ECOG 0-2
• See Disease Characteristics
• Bilirubin less than 3 times upper limit of normal (ULN)
• AST and ALT less than 3 times ULN
• Creatinine less than 2 times ULN
• No New York Heart Association class III or IV heart disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and at least 3 months after study for male patients
• See Disease Characteristics
• No prior allogeneic bone marrow or peripheral blood stem cell transplantation
• At least 48 hours since prior interferon alfa
• At least 24 hours since prior hydroxyurea
• At least 6 weeks since prior busulfan
• No other prior chemotherapy for blast crisis (except hydroxyurea)
• Concurrent hydroxyurea or anagrelide for severe leukocytosis or thrombocytosis allowed
• At least 4 weeks since prior investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (imatinib mesylate, cytarabine); Patients who have not previously received imatinib mesylate receive oral imatinib mesylate daily on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive cytarabine IV over 2 hours every 12 hours on days 29-32. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity.

Drug: cytarabine; Given IV; Other Names: Cytosar-U; cytosine arabinoside; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Drug: imatinib mesylate; Given PO; Other Names: Gleevec; CGP 57148; Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity according to NCI/NIH Common Toxicity Criteria	Described by duration, relatedness to treatment, and action taken.	Up to 2 years
Hematologic response		Up to 6 months
Bone marrow cytogenetic response		Up to 6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ronald Paquette, University of California at Los Angeles (UCLA )

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): April 1, 2003

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; 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; Protein Kinase Inhibitors; Cytarabine; Imatinib Mesylate
• Other Study ID Numbers: NCI-2012-02374; UCLA-0011009; CDR0000068441 (Registry Identifier: PDQ (Physician Data Query))