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

NCT00644878 | Terminated Phase 2 Results

• 1 other identifier: CAMN107AUS09
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 11

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

Conditions

Chronic Myelogenous Leukemia - Chronic Phase

Keywords

leukemia; chronic myelogenous leukemia; chronic phase; molecular response; nilotinib; ENABL

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of Participants Who Achieved Major Molecular Response (MMR)

  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

  From Baseline up to 12 Months

• Median Time to Best Molecular Response

  From Start of Study up to End of the Study (up to 41 Months)

• Duration of Best Molecular Response

  From Start of Study up to End of the Study (up to 41 Months)

• Number of Participants With an Event-free Survival

  From Start of Study up to End of the Study (up to 41 Months)

Study Arms (1)

Nilotinib

EXPERIMENTAL

Drug: Nilotinib

Interventions

Nilotinib DRUG

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.

Also known as: Tasigna, AMN 107

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

USC Norris Cancer Center Jane Anne Nohl

Los Angeles, California, 90033, United States

Location

Georgia Health Sciences University Dept. of MCG

Augusta, Georgia, 30912, United States

Location

Indiana Blood and Marrow Institute

Beech Grove, Indiana, 46107, United States

Location

University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic

Iowa City, Iowa, 52242, United States

Location

LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center

New Orleans, Louisiana, 70115, United States

Location

St. Agnes Hospital

Baltimore, Maryland, 21229, United States

Location

Cancer Centers of the Carolinas

Greenville, South Carolina, 29615, United States

Location

South Texas Institute of Cancer

Corpus Christi, Texas, 78405, United States

Location

Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr

Houston, Texas, 77030, United States

Location

Central Utah Clinic Central Utah Clinic (7)

Provo, Utah, 84604, United States

Location

Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 28042454 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated on 31 March 2012 due to slower than planned enrollment, resulting in a small sample size, no inferential analyses were conducted.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2008
• First Posted: March 27, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: August 18, 2021
• Results First Posted: August 18, 2021

Record last verified: 2021-07

Locations

US (11)