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

NCT00171223 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CSTI571A0110E22005-001382-33
• Study Type: interventional
• Target: 532
• Locations: 6 countries
• Sites: 28

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

Keywords

Chronic Myelogenous Leukemia; CML; Philadelphia Chromosome; Accelerated phase; Acute Myelogenous Leukemia; AML; Acute Lymphoblastic Leukemia; ALL; Imatinib mesylate

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571

  Response was evaluated from bone marrow aspirates and biopsy samples. Bone marrow cytogenetic studies were performed every 3 months during the core phase of the study, then twice yearly, then annually to evaluate Philadelphia chromosome positive (Ph+). Cytogenetic response was defined as the best response the participant achieved during study. Based on the percentage of Ph+ cells = (positive cells/ examined cells) x100, at each BM assessment the cytogenetic response was classified as: Complete Cytogenetic Response (CCyR):, 0% Ph+ cells; Partial Cytogenetic Response (PCyR):, \>0 - 35% Ph+ cells; Minor: \>35 - 65% Ph+ cells; and Minimal: \>65 - 95% Ph+ cells, None: \>95 % Ph+ cells and Not done: \<20 metaphases were examined and/or response could not be assigned. Major Cytogenetic Response (MCyR) was defined as sum of the CCyR plus PCyR rates.

  Up to 6 years after the start of treatment

Secondary Outcomes (6)

• Percentage of Participants With Complete Hematologic Response to STI571

  12 months after the start of treatment

• Duration of Complete Hematologic Response to STI571

  12 months after the start of treatment

• Time to Complete Hematologic Response to STI571

  12 months after the start of treatment

• Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms

  Up to 9 months after the start of treatment

• Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status

  Up to 9 months after the start of treatment

Study Arms (1)

All Participants With Chronic Myeloid Leukemia

EXPERIMENTAL

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).

Drug: STI571

Interventions

STI571 DRUG

STI571 oral capsules or tablets.

Also known as: Imatinib Mesylate

All Participants With Chronic Myeloid Leukemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (28)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

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

Tampa, Florida, 33612, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Oncology Center

Baltimore, Maryland, 21231, United States

Location

Dana Faber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Kamanos Cancer Center

Detroit, Michigan, 48201, United States

Location

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

St Louis, Missouri, 63110, United States

Location

New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Oregon Health & sciences University

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center, University of Texas

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Lille, France

Location

Novartis Investigative Site

Pessac, France

Location

Novartis Investigative Site

Poitiers, France

Location

Novartis Investigative Site

Frankfurt, Germany

Location

Novartis Investigative Site

Leipzig, Germany

Location

Novartis Investigative Site

Mainz, Germany

Location

Novartis Investigative Site

Mannheim, Germany

Location

Novartis Investigative Site

Bologna, Italy

Location

Novartis Investigative Site

Milan, Italy

Location

Novartis Investigative Site

Monza, Italy

Location

Novartis Investigative Site

Orbassano, Italy

Location

Novartis Investigative Site

Pavia, Italy

Location

Novartis Investigative Site

Rome, Italy

Location

Novartis Investigative Site

Udine, Italy

Location

Novartis Investigative Site

Basel, Switzerland

Location

Novartis Investigative Site

London, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Translocation, Genetic; Chromosome Aberrations; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: December 6, 1999
• Primary Completion: November 29, 2013
• Study Completion: November 29, 2013
• Last Updated: July 22, 2021
• Results First Posted: July 22, 2021

Record last verified: 2021-07

Locations

CH (1); DE (4); US (11); FR (3); IT (7); GB (2)