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

Chronic Myelogenous Leukemia in Chronic Phase Clinical Trial

— MACS1428  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227577
• Other study ID #: CAMN107AUS28
• Status: Completed
• Phase: Phase 4
• First received: October 21, 2010
• Last updated: January 11, 2016
• Start date: November 2010
• Est. completion date: November 2014

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myelogenous Leukemia in Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Nilotinib
Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Confirmed Complete Molecular Response (CMR)	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.	4 years	No
Secondary	Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)	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.	4 years	No
Secondary	Time to CMR, CCyR and MMR	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.	4 years	No
Secondary	Duration of CMR, CCyR and MMR	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.	4 years	No
Secondary	Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)	Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.	4 years	No
Secondary	Time to Progression of AP/BC	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.	4 years	No
Secondary	Number of Participants With Loss of CCyR, MMR and CMR	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.	4 years	No
Secondary	Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.	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.	4 years	No
Secondary	Event-free Survival, Progression-free Survival and Overall Survival	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.	4 years	No