CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib (MACS1428)

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)

"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."

Study Overview

• Status: Completed
• Conditions: Chronic Myelogenous Leukemia in Chronic Phase
• Intervention / Treatment: Drug: Nilotinib

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
    • Burbank, California, United States, 91505-6866
      • Providence St. Joseph Medical Center Roy&Patricia Disney Fam Cancer
    • Concord, California, United States, 94520
      • Bay Area Cancer Research Dept.ofBayAreaCancerResearch
    • Yorba Linda, California, United States, 92886
      • St. Jude Heritage Medical Group Virginia Crosson Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Sarah Cannon Research Institute SCRI
    • Miami, Florida, United States, 33176
      • Advanced Medical Specialties
    • New Port Richey, Florida, United States, 34652
      • Pasco Hernando Oncology
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University MedCollege of GA Cancer Ctr 2
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • Stroger Cook County Hospital Division of Hematology & Onc
  • Indiana
    • Beach Grove, Indiana, United States, 46107
      • Indiana Blood and Marrow Institute
  • Kansas
    • Witchita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center(3)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis University Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center University of Nebraska Med Ctr
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Ct James P Wilmot Cancer Ctr
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Duke University Med Ctr
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health & Science University
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Sarah Cannon Research Inst.
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Research Institute Baylor Research Institute (17)
    • Houston, Texas, United States, 77090
      • Millennium Oncology
    • Houston, Texas, United States, 77024
      • Oncology Consultants Oncology Consultants, P.A.
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib; Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.	Drug: Nilotinib; Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Berdeja JG, Heinrich MC, Dakhil SR, Goldberg SL, Wadleigh M, Kuriakose P, Cortes J, Radich J, Helton B, Rizzieri D, Paley C, Dautaj I, Mauro MJ. Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis. Leuk Lymphoma. 2019 Oct;60(10):2384-2393. doi: 10.1080/10428194.2019.1590569. Epub 2019 Mar 26.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: October 21, 2010
• First Submitted That Met QC Criteria: October 21, 2010
• First Posted (Estimate): October 25, 2010

Study Record Updates

• Last Update Posted (Estimate): February 8, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Leukemia; Nilotinib; CML; Chronic Myelogenous Leukemia; CML-CP
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: CAMN107AUS28