CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib

Phase 4

Completed

Conditions: Chronic Myelogenous Leukemia in Chronic Phase

Interventions: Drug: Nilotinib

Registration Number: NCT01227577

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: "This is a single-arm, open-label, multi-center study of complete molecular response (CMR) in adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP). The study is designed to evaluate early and deep molecular responses up to 4 years on nilotinib treatment. The primary end point is Rate of confirmed CMR in newly diagnosed Philadelphia chromosome positive CML-CP patients."

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 128

Inclusion Criteria

Patients with Ph+ CML-CP within 3 months of diagnosis. Male or female patients' ≥ 18 years of age. Patients must have adequate end organ function.

Exclusion Criteria

Previously documented T315I mutation. Other CML treatment is an exclusion criteria with the following exception: While awaiting study start, patients may be treated with anagrelide (no treatment duration limit), hydroxyurea (no treatment duration limit), and/or up to a 14 day supply of a tyrosine kinase inhibitor (TKI) approved by the FDA for frontline treatment. Patients taking a TKI prior to study entry must have at least a one day washout from their last dose of medication and have recovered from any side effects of such therapy.

Impaired cardiac function as defined by the protocol. Patients with contraindications to receiving nilotinib, including concomitant medications.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nilotinib	Nilotinib	Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Confirmed Complete Molecular Response (CMR)	4 years	CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)	4 years	Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)	4 years	CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.
Time to CMR, CCyR and MMR	4 years	Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.
Duration of CMR, CCyR and MMR	4 years	Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.
Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.	4 years	CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Event-free Survival, Progression-free Survival and Overall Survival	4 years	Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.
Time to Progression of AP/BC	4 years	Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.
Number of Participants With Loss of CCyR, MMR and CMR	4 years	Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.

Trial Locations

Locations (32): Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
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Hackensack, New Jersey, United States
Advanced Medical Specialties
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Miami, Florida, United States
Louis A. Weiss Memorial Hospital
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Chicago, Illinois, United States
Dana Farber Cancer Institute
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Boston, Massachusetts, United States
Henry Ford Hospital
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Detroit, Michigan, United States
Duke University Medical Center Duke University Med Ctr
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Durham, North Carolina, United States
Tennessee Oncology Sarah Cannon Research Inst.
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Nashville, Tennessee, United States
Oncology Consultants Oncology Consultants, P.A.
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Houston, Texas, United States
Providence St. Joseph Medical Center Roy&Patricia Disney Fam Cancer
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Burbank, California, United States
Baylor Research Institute Baylor Research Institute (17)
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Dallas, Texas, United States
Sarah Cannon Research Institute SCRI
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Jacksonville, Florida, United States
Bay Area Cancer Research Dept.ofBayAreaCancerResearch
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Concord, California, United States
Indiana Blood and Marrow Institute
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Beach Grove, Indiana, United States
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center(3)
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New Orleans, Louisiana, United States
University of Maryland
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Baltimore, Maryland, United States
St. Louis University Cancer Center
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St. Louis, Missouri, United States
The Jones Clinic
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Germantown, Tennessee, United States
Millennium Oncology
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Houston, Texas, United States
University of Virginia
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Charlottesville, Virginia, United States
Pacific Cancer Medical Center, Inc.
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Anaheim, California, United States
Stroger Cook County Hospital Division of Hematology & Onc
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Chicago, Illinois, United States
St. Jude Heritage Medical Group Virginia Crosson Cancer Center
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Yorba Linda, California, United States
Georgia Regents University MedCollege of GA Cancer Ctr 2
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Augusta, Georgia, United States
University of Nebraska Medical Center University of Nebraska Med Ctr
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Omaha, Nebraska, United States
Cancer Center of Kansas
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Witchita, Kansas, United States
Oregon Health & Science University
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Portland, Oregon, United States
Pasco Hernando Oncology
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New Port Richey, Florida, United States
University of Rochester Medical Ct James P Wilmot Cancer Ctr
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Rochester, New York, United States
Providence Regional Cancer Partnership
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Everett, Washington, United States
Cancer Centers of the Carolinas Cancer Center
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Greenville, South Carolina, United States
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
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Chattanooga, Tennessee, United States
Montefiore Medical Center
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Bronx, New York, United States