Imatinib Mesylate Plus Cytarabine in Treating Patients With Chronic Myelogenous Leukemia

A Phase II Study To Determine The Anti-Leukemic Effects Of STI571 In Combination With Ara-C In Patients With Chronic Myelogenous Leukemia In Chronic Phase

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This phase II trial is studying giving imatinib mesylate together with cytarabine to see how well it works in treating patients with chronic phase chronic myelogenous leukemia.

Study Overview

• Status: Terminated
• Conditions: Leukemia
• Intervention / Treatment: Drug: cytarabine; Drug: imatinib mesylate

Detailed Description

OBJECTIVES:

• Determine the rate and duration of complete or major and minor cytogenetic responses after 6 and 12 months of treatment in patients with chronic phase chronic myelogenous leukemia treated with imatinib mesylate and cytarabine.
• Determine the rate and duration of complete hematologic responses after 6 and 12 months of treatment in patients treated with this regimen.
• Determine the rate of molecular response in patients with a complete cytogenetic response after 6 and 12 months of treatment with this regimen.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the safety of this regimen in these patients.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive oral imatinib mesylate on days 1-28 and cytarabine subcutaneously on days 15-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.

Patients are followed for 30-60 days.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Cytogenetically confirmed chronic phase chronic myelogenous leukemia (CML)

  • Less than 15% blasts in peripheral blood or bone marrow
  • Less than 30% blasts and promyelocytes in peripheral blood or bone marrow
  • Less than 20% basophils in blood or bone marrow
  • Platelet count at least 100,000/mm^3
• Philadelphia chromosome positive
• No more than 6 months since initial diagnosis
• No presence of leukemia beyond the bone marrow, blood, liver, or spleen (i.e., chloroma)
• Refused allogeneic stem cell transplantation as first-line therapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
• No other serious uncontrolled medical condition
• No history of noncompliance to medical regimens or potential unreliability

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior biologic therapy for CML

Chemotherapy:

• No prior chemotherapy for CML except hydroxyurea
• Concurrent hydroxyurea to control blood counts during first 3 months of treatment allowed
• No other concurrent chemotherapy

Endocrine therapy:

• No prior endocrine therapy for CML

Radiotherapy:

• No prior radiotherapy for CML

Surgery:

• Not specified

Other:

• More than 28 days since prior investigational anticancer agents
• Prior anagrelide hydrochloride for CML allowed
• Concurrent anagrelide hydrochloride to control blood counts during first 3 months of treatment allowed
• No concurrent grapefruit juice or grapefruit

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: Cytarabine/ Imatinib Mesylate	Drug: cytarabine; Once daily subcutaneous injection of Ara-C (Cytarabine) at a dose of 20 mg (10 mg or 5 mg if they have been dose reduced) per square meter of calculated body surface area, on days 15-28 of each sequential 28 day cycle; Drug: imatinib mesylate; Once daily oral administration of STI571 (Imatinib Mesylate) at a dose of 400 mg for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Rate of Major Cytogenetic Response at 6 Months	Cytogenetic response is defined in terms of the percentage of Philadelphia (Ph) chromosome. Major cytogenetic response is defined as 0-34% Ph-positive cells.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The Rate of Complete Cytogenetic Response at 6 Months	6 months
The Rate of Complete and Major Cytogenetic Responses at 12 Months	12 months
The Rate of Minor Cytogenetic Responses at 6 and 12 Months	6 and 12 months
The Rate of Complete Hematologic Responses at 6 and 12 Months	6 and 12 months

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Brian J. Druker, MD, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2001
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; 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; Protein Kinase Inhibitors; Cytarabine; Imatinib Mesylate
• Other Study ID Numbers: CDR0000068822; OHSU-NCI-4653; OHSU-1184 (Other Identifier: OHSU IRB); OHSU-HEM-01017-LX (Other Identifier: OHSU Knight Cancer Institute); NCI-4653