Clinical trial NCT00644878: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myelogenous Leukemia - Chronic Phase
Keywords: leukemia
chronic myelogenous leukemia
chronic phase
molecular response
nilotinib
ENABL
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-03-27
Enrollment: 18
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: 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


Eligibility criteria: 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

Primary outcomes:
measure: Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels
timeFrame: From Baseline up to 12 Months
Secondary outcomes:
measure: Number of Participants Who Achieved Major Molecular Response (MMR)
timeFrame: From Baseline up to 12 Months
measure: Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12
timeFrame: From Baseline up to 12 Months
measure: Median Time to Best Molecular Response
timeFrame: From Start of Study up to End of the Study (up to 41 Months)
measure: Duration of Best Molecular Response
timeFrame: From Start of Study up to End of the Study (up to 41 Months)
measure: Number of Participants With an Event-free Survival
timeFrame: From Start of Study up to End of the Study (up to 41 Months)
measure: Number of Participants With a Progression-free Survival
timeFrame: From Start of Study up to End of the Study (up to 41 Months)
measure: Number of Participants With an Overall Survival
timeFrame: From Start of Study Enrollment up to End of the Study (up to 41 Months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Cancer Center Jane Anne Nohl
state: California
city: Augusta
country: United States
facility: Georgia Health Sciences University Dept. of MCG
state: Georgia
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Institute
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
state: Iowa
city: New Orleans
country: United States
facility: LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: St. Agnes Hospital
state: Maryland
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Corpus Christi
country: United States
facility: South Texas Institute of Cancer
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
state: Texas
city: Provo
country: United States
facility: Central Utah Clinic Central Utah Clinic (7)
state: Utah
city: Milwaukee
country: United States
facility: Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial
state: Wisconsin
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.