Study of Molecular Response in Adult Patients on Nilotinib With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Ph+ CML) in Chronic Phase and a Suboptimal Molecular Response to Imatinib (MACS0254)

A Multi-center, Open-label, Exploratory Study of Bcr-Abl Kinetics in Adult Patients on Nilotinib With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) and a Suboptimal Molecular Response to Imatinib

This exploratory study will evaluate the change in molecular response in chronic myelogenous leukemia - chronic phase patients with a complete cytogenetic response and have a suboptimal molecular response to imatinib

Study Overview

• Status: Terminated
• Conditions: Chronic Myelogenous Leukemia - Chronic Phase
• Intervention / Treatment: Drug: Nilotinib

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center Jane Anne Nohl
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University Dept. of MCG
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Indiana Blood and Marrow Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Cancer Centers of the Carolinas
  • Texas
    • Corpus Christi, Texas, United States, 78405
      • South Texas Institute of Cancer
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
  • Utah
    • Provo, Utah, United States, 84604
      • Central Utah Clinic Central Utah Clinic (7)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial

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

Select Inclusion Criteria:

• Male or female patients ≥ 18 years of age with a confirmed diagnosis of Ph+ CML-CP and CCyR

• A suboptimal molecular response to imatinib defined as:

  • Group 1: Treated with 1 year of imatinib, complete cytogenetic response (CCyR) but no major molecular response (MMR) (Bcr-Abl levels >0.1%IS);
  • Group 2: No specific duration of imatinib required, achieved CCyR but has >1 log increase in Bcr-Abl transcript levels
• Adequate end organ function
• Patients must have had an imatinib washout period of at least 3 days and not to exceed 7 days prior to the first dose of nilotinib. Group 1 patients must have been treated with imatinib for at least 1 year. There was no imatinib treatment duration requirement for Group 2 patients.
• For Group 1, patients were eligible for screening if they were treated with an imatinib dose of at least 400mg daily. Dose reduction could have occurred as long as the minimum dose was 300mg daily and the reduction lasted ≤ 28 days. The patient was required to be on 400 mg daily (or a higher dose) of imatinib for at least 6 consecutive months leading up to screening for this study.
• For Group 2 patients, dose reduction while on imatinib could have occurred as long as the minimum dose was 300 mg daily, and the reduction lasted ≤28 days.

Select Exclusion Criteria:

• Prior accelerated phase or blast crisis CML
• Patients achieving prior CCyR on imatinib who lost cytogenetic response prior to entering study
• Previously documented T315I mutations
• Prior therapy with any other tyrosine kinase inhibitor except imatinib
• 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	Drug: Nilotinib; Nilotinib 300 mg is taken by mouth twice a day at 12 hour intervals. Nilotinib is to be taken with water on an empty stomach. No food two hours prior to the dose of nilotinib and for one hour following the dose.; Other Names: AMN 107; Tasigna

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels	The change on a logarithmic scale at 12 months from a standardized baseline value (100% on the international scale [IS]) in Bcr-Abl transcripts as assessed by peripheral blood Quantitative real-time polymerase chain reaction (RQ-PCR).	From Baseline up to 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Major Molecular Response (MMR)	Major Molecular Response (MMR) value at molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized InteYesrferon versus STI571 (IRIS) study or 0.1 percent (%) per International Scale (IS).	From Baseline up to 12 Months
Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12	Number of participants experiencing either a greater than or equal to (>or=) 1, >or= 2, or >or= 3 log10 reduction in Bcr-Abl transcript levels from Baseline to End of Cycle (EOC) 45 (Day1219 - Day1302) were presented.	From Baseline up to 12 Months
Median Time to Best Molecular Response	The median time to best molecular response, defined as the time (in months) from the date of enrollment to the date when the maximum reduction in Bcr-Abl transcript level was observed.	From Start of Study up to End of the Study (up to 41 Months)
Duration of Best Molecular Response	Duration of best molecular response, defined as the time (in months) from the date of best molecular response to a date when an increase in >1 log10 was observed	From Start of Study up to End of the Study (up to 41 Months)
Number of Participants With an Event-free Survival	Event-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of any of the following: loss of complete hematological response (CHR), loss of Complete cytogenetic response (CCyR), >1 log increase in Bcr-Abl transcripts from the lowest recorded value, progression to accelerated or blast phase, and death.	From Start of Study up to End of the Study (up to 41 Months)
Number of Participants With a Progression-free Survival	Progression-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of progression to Accelerated phase (AP) or Blast crisis (BC) phase, chronic myelogenous leukemia (CML) or death. Participants who did not have an event or dropped out without an event are considered censored at the date of the last observed event.	From Start of Study up to End of the Study (up to 41 Months)
Number of Participants With an Overall Survival	Overall survival was defined as the number of participants from enrollment to the date of death.	From Start of Study Enrollment up to End of the Study (up to 41 Months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Ailawadhi S, Akard LP, Miller CB, Jillella A, DeAngelo DJ, Ericson SG, Lin F, Warsi G, Radich J. Exploratory study on the impact of switching to nilotinib in 18 patients with chronic myeloid leukemia in chronic phase with suboptimal response to imatinib. Ther Adv Hematol. 2017 Jan;8(1):3-12. doi: 10.1177/2040620716678118. Epub 2016 Nov 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: March 19, 2008
• First Submitted That Met QC Criteria: March 26, 2008
• First Posted (Estimate): March 27, 2008

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: leukemia; chronic myelogenous leukemia; nilotinib; chronic phase; molecular response; ENABL
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Philadelphia Chromosome
• Other Study ID Numbers: CAMN107AUS09