An Extension Study to Determine the Efficacy and Safety of STI571 in Participants With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha

NCT ID: NCT00171223

Last Updated: 2021-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 532 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-12-06
• Study Completion Date: 2013-11-29

Brief Summary

During the Core Phase of the study, participants received STI571 at a dose of 400 milligrams (mg) daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study provided that, in the opinion of the investigator, they had benefited from treatment with STI571 and there were no safety concerns.

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Participants With Chronic Myeloid Leukemia

Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 mg. During the Core Phase of the study, participants received STI571 daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study, and they continued STI571 for as long as the therapy was beneficial or until death, intolerable toxicity or the decision to discontinue by the investigator, whichever came first. (Maximum duration on study was approximately 14 years).

Group Type: EXPERIMENTAL

STI571

Intervention Type: DRUG

STI571 oral capsules or tablets.

Interventions

STI571

STI571 oral capsules or tablets.

Intervention Type: DRUG

Other Intervention Names

Imatinib Mesylate

Eligibility Criteria

Inclusion Criteria

Participants included in the study were:

• Consenting males or females greater than or equal to (≥)18 years of age with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML).
• With a documented failure of interferon-alpha (IFN) or an IFN-containing therapy, characterized as resistance or refractoriness defined as any of the following:

• Hematologic Resistance - Failure to achieve a complete hematological response (CHR), lasting for at least 1 month despite 6 or more months of IFN or an IFN-containing regimen, in which IFN was administered at a dose of at least 25 million international units (MIU) per week. During this treatment period the cumulative duration of hydroxyurea therapy may not have exceeded 50% of the treatment period with the IFN-containing regimen.
• Cytogenetic Resistance - Bone marrow cytogenetics showing ≥65% Ph+ after one year of IFN-based therapy,
• Cytogenetic Refractoriness - An increase in the Ph+ chromosome in BM cells by at least 30 percentage points (e.g. from 20% to 50%, or from 30% to 60%) confirmed by two samples at least 1 month apart, or an absolute increase to ≥65%,
• Hematologic Refractoriness - A rising white blood cell count (WBC) [to a level ≥20 x 10^9/L confirmed by two samples taken at least two weeks apart] for participants achieving a complete hematologic response while receiving IFN or an IFN-containing regimen. This regimen must have included IFN at a dose of at least 25 MIU administered per week. During this treatment period the cumulative duration of hydroxyurea therapy may not have exceeded 50% of the treatment period with the IFN-containing regimen.

In this report all refractory populations were referred to as "relapsed" populations.

• With a documented intolerance to IFN therapy defined as a ≥Grade 3 non-hematologic toxicity persisting for at least one month, for participants receiving IFN or an IFN- containing regimen. IFN was to be administered at a dose of at least 25 MIU/week. Participants who were intolerant of IFN were to have been diagnosed ≥6 months prior to the time of entry into the study.

Exclusion Criteria

Participants excluded from the study were:

• Females of childbearing potential without a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions were to be used throughout the trial in both sexes.
• With serum bilirubin and creatinine concentrations more than twice the upper limit of the normal range (ULN).
• With serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) more than twice the ULN.
• With >15% of blasts or basophils in peripheral blood (PB) or bone marrow (BM).
• With ≥30% of blasts plus promyelocytes in PB or BM.
• With a platelet count of less than (<)100 x 10^9/L.
• With an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥3.
• Receiving busulfan within 6 weeks of Day 1.
• Receiving treatment with IFN or cytosine arabinoside (Ara-C) within 14 days of Day 1.
• Receiving treatment with hydroxyurea within 7 days of Day 1.
• Receiving other investigational agents within 28 days of Day 1.
• With prior marrow or stem cell transplantation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

UCLA Medical Center

Los Angeles, California, United States

H. Lee Moffet Cancer Center & Research Institute/Univ of South Florida

Tampa, Florida, United States

Northwestern Univ meical School/Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Dana Faber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Wayne State University/Kamanos Cancer Center

Detroit, Michigan, United States

C/O V. Ward - Washington Univ. school of Medicine

St Louis, Missouri, United States

New York Presbyterian Hospital

New York, New York, United States

Oregon Health & sciences University

Portland, Oregon, United States

MD Anderson Cancer Center, University of Texas

Houston, Texas, United States

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Pessac, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Leipzig, , Germany

Novartis Investigative Site

Mainz, , Germany

Novartis Investigative Site

Mannheim, , Germany

Novartis Investigative Site

Bologna, , Italy

Novartis Investigative Site

Milan, , Italy

Novartis Investigative Site

Monza, , Italy

Novartis Investigative Site

Orbassano, , Italy

Novartis Investigative Site

Pavia, , Italy

Novartis Investigative Site

Rome, , Italy

Novartis Investigative Site

Udine, , Italy

Novartis Investigative Site

Basel, , Switzerland

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Countries

United States; France; Germany; Italy; Switzerland; United Kingdom

Other Identifiers

2005-001382-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSTI571A0110E2

Identifier Type: -

Identifier Source: org_study_id