Clinical trial NCT00171223: 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
Official title: An Extension to a Phase II Study to Determine the Efficacy and Safety of STI571 in Patients With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 532
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571
timeFrame: Up to 6 years after the start of treatment
Secondary outcomes:
measure: Percentage of Participants With Complete Hematologic Response to STI571
timeFrame: 12 months after the start of treatment
measure: Duration of Complete Hematologic Response to STI571
timeFrame: 12 months after the start of treatment
measure: Time to Complete Hematologic Response to STI571
timeFrame: 12 months after the start of treatment
measure: Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms
timeFrame: Up to 9 months after the start of treatment
measure: Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Up to 9 months after the start of treatment
measure: Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates
timeFrame: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffet Cancer Center & Research Institute/Univ of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern Univ meical School/Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Kamanos Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: C/O V. Ward - Washington Univ. school of Medicine
state: Missouri
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Portland
country: United States
facility: Oregon Health & sciences University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center, University of Texas
state: Texas
city: Lille
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
city: Orbassano
country: Italy
facility: Novartis Investigative Site
city: Pavia
country: Italy
facility: Novartis Investigative Site
city: Rome
country: Italy
facility: Novartis Investigative Site
city: Udine
country: Italy
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: