Late Chronic Phase Chronic Myelogenous Leukemia

Therapy of Late Chronic Phase Chronic Myelogenous Leukemia (CML) With High-Dose Gleevec (STI571)

Objectives:

Primary endpoints:

To achieve low levels of Polymerase Chain Reaction (PCR) ratios of B-cell antigen receptor (Bcr-Abl)/Bcr (molecular CR) in a significant proportion of patients after 12 months of higher doses (800 mg daily) of Gleevec therapy To increase the proportion of patients achieving a complete cytogenetic response in patients with Ph-positive chronic phase CML using initial higher dose Gleevec therapy.

Secondary endpoints:

To evaluate the durations of PCR negativity, cytogenetic response, hematologic control, and survival.

To analyze differences in response rates and in prognosis within different risk groups and patient characteristics

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: Gleevec

Detailed Description

Treatment: Imatinib mesylate is a new oral medication that blocks a protein that is responsible for CML

Patients on this study will take 400 mg of imatinib twice daily (morning and evening). If you have side effects, the dose may be lowered. If you are taking less than 800 mg of imatinib, you can take your dose once per day or divided in two doses. Imatinib mesylate should be taken with a large glass of water.

After completing 3 to 12 months of therapy, response to imatinib mesylate will be evaluated. Treatment may be continued for up to 20 years, or as long as it is judged best to control the leukemia.

Update June 2010:

Blood tests are recommended 2 times per year. Your doctor will discuss with you how often you should have blood tests. Bone marrow will be done if your doctor thinks it is necessary to check your disease. You must return to M. D. Anderson at least once every year. You may not need a bone marrow test every visit, but you will have blood drawn to measure the amount of disease you have. If the leukemia cannot be found for 2 years or longer on the blood test called PCR which is done to measure the amount of disease you have, your doctor may talk to you about stopping treatment with imatinib. If you and your doctor decide to stop your therapy, you will have a blood test for PCR done every 3 to 6 months. You do not need to return to M. D. Anderson to have this blood test done. You may have the blood taken by your local doctor and mailed to M. D. Anderson. If the leukemia is found again by the PCR blood test, your doctor may recommend that you restart treatment with imatinib. You may decide to stay on treatment with imatinib even if your PCR blood test does not show any sign of leukemia for 2 years or longer.

This is an investigational study. The FDA has authorized the use of imatinib mesylate for patients with CML. It is the dose of imatinib mesylate being used that is investigational. A total of 50 patients will take part in this study. All will be enrolled at M.D. Anderson.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University Of MD Anderson Cancer Center

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

Inclusion Criteria:

1. Patients age 15 years or older with a diagnosis of Ph-positive or Bcr-positive CML in chronic phase CML. They should be in at least one of the categories below: A. Patients must have received interferon alpha and: - Failed to achieve or lost a hematologic complete remission(after 3 months of therapy with interferon), or - Failed to achieve or lost a major cytogenetic remission, or - Failed to achieve or lost a complete molecular remission (competitive quantitative PCR <0.05%), or - Were intolerant to interferon B. Patients in late chronic phase (i.e., >/= 12 months from diagnosis) who have not received treatment with interferon and: - Have high risk for toxicity with IFN-A (e.g., age >/= 60 years), or - Refuse to use IFN-A
2. ECOG performance of 0-2.
3. Serum bilirubin less than 2mg%, serum creatinine less than 2mg%.

Exclusion Criteria:

1. - NYHA Class 3-4 heart disease; Pregnant or lactating females
2. Women of pregnancy potential must practice contraception
3. Patients in accelerated phase (except clonal evolution) or blastic phase are excluded. - Patients with clonal evolution as their only criterion for accelerated phase are eligible.
4. Inclusion of women and minorities: As per NIH policy, women and members of minorities will be included in this protocol as they are referred in the CML population.

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: Gleevec; Gleevec 400 mg by mouth (P.O.) twice daily = 800 mg total daily dose	Drug: Gleevec; 400 mg P.O. twice daily (800 mg total daily dose); Other Names: STI571

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytogenetic Complete Response (CR) Rate	CR Rate = Number participants out of total treated with complete cytogenetic response. Complete Hematologic Remission (CHR) - normalization >4 weeks of bone marrow (less than 5% blasts) & peripheral blood with white blood count (WBC)<10x10^9/L & no peripheral blasts, promyelocytes or myelocytes, disappearance of all signs & symptoms of disease. Partial Hematologic Response (PHR) = CHR except persistence of immature cells (myelocytes, metamyelocytes), or splenomegaly <50% of pretreatment, or thrombocytosis >450x10^9/L but <50% of pretreatment. Complete hematologic remission further classified according to suppression of Philadelphia chromosome (Ph) by cytogenetics or fluorescence in situ hybridization (FISH): a) No cytogenetic response - Ph positive 100% of pretreatment value; b) Minor cytogenetic response - Ph positive 35-90% of pretreatment value; c) Partial cytogenetic response - Ph positive 1-34% of pretreatment value; d) Complete cytogenetic response - Ph positive 0%.	Evaluated at 6 months; Polymerase Chain Reaction (PCR) testing for BCR-ABL every 3-4 months in year one then every year.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Jorge E Cortes, MD, The University Of MD Anderson Cancer Center

Publications and helpful links

Helpful Links

• UT MD Anderson Cancer Center web site

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: March 23, 2010
• First Submitted That Met QC Criteria: March 23, 2010
• First Posted (Estimate): March 25, 2010

Study Record Updates

• Last Update Posted (Estimate): May 11, 2016
• Last Update Submitted That Met QC Criteria: May 9, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Gleevec; Leukemia; CML; Chronic Myelogenous Leukemia; STI571
• 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; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: ID01-292