Clinical trial NCT00980018: An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
Official title: An Exploratory Trial to Assess the Improvement of Chronic Low-grade Non-hematologic Adverse Events Experienced by Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Treated With Imatinib When Switched to Nilotinib Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Myelogenous Leukemia
Keywords: CML
Leukemia
Tasigna
nilotinib
AMN107
CML-CP
Chronic Phase
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-09-18
Enrollment: 52
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: The purpose of this exploratory study will be to examine changes in chronic low grade chronic adverse events, measured by Common Terminology Criteria for Adverse Events (CTCAE) grading, when patients are switched from imatinib to nilotinib therapy.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 18 years of age
2. Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
3. Diagnosis of CML-CP associated with Bcr-Abl quantifiable by RQ-PCR (IS)
4. Patients must be an imatinib responder and achieved the following efficacy milestones as appropriate for the length of time on imatinib therapy as per protocol
5. CML-CP patients initiated on any dose of imatinib
6. Ability to provide written informed consent prior to any study related screening procedures being done

Exclusion Criteria:

1. Loss of CHR or cytogenetic response
2. Prior accelerated phase or blast phase CML
3. Previously documented T315I mutation
4. Presence of chromosomal abnormalities (trisomy 8) and/or clonal evolution other than Ph+.
5. Previous treatment with any other tyrosine kinase inhibitor except for imatinib.
6. Treatment with other investigational agents within 30 days of Day 1.
7. History of non-compliance to medical regimens or inability to grant consent.
8. Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Percentage of Participants With Improvement in Imatinib Related Chronic Low Grade Non Hematologic Adverse Event (AE) After Switch to Treatment With Nilotinib at End of Cycle 3
timeFrame: End of Cycles 1, 2, and 3
Secondary outcomes:
measure: Percentage of Participants Achieving Complete Cytogenetic Response (CCyR) After Switching to Nilotinib for Participants Not Reporting CCyR at Baseline
timeFrame: Cycles 1, 2, 6, 9, and 12
measure: Percentage of Participants Achieving Major Molecular Response (MMR) After the Switch in the Therapy for Participants Not Reporting MMR at Baseline
timeFrame: Cycles 1,2,3,6,9,12
measure: Log Change in BCR-Abl Transcript Level From Baseline After the Switch Therapy
timeFrame: Cycles 1,2,3,6,9, and 12
measure: Duration of Complete Cytogenetic Response
timeFrame: 18 months of follow up from the first documented response
measure: Time to Complete Cytogenetic Response in Participants Not Reporting at Baseline
timeFrame: Cycle 12
measure: Duration of Major Molecular Response
timeFrame: 18 months of follow up from the first documented response
measure: Time to Major Molecular Response (MMR) in Participants With MMR Absent at Baseline
timeFrame: Cycles 1,2,3,6,9,12
measure: Time to Optimal Imatinib-related Adverse Event Improvement
timeFrame: 18 months of follow up from the date of the first dose of study drug to the time to maximum decrease in CTCAE grade of these events
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Little Rock
country: United States
facility: Hematology Oncology Services of Arkansas SC
state: Arkansas
city: Los Angeles
country: United States
facility: USC Norris Cancer Center LAC & USC Medical Center
state: California
city: Poway
country: United States
facility: Southwest Cancer Care Murrieta
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC - Aurora
state: Colorado
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
state: Florida
city: Chicago
country: United States
facility: Stroger Cook County Hospital John H. Stroger Hospital
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers IndianaBlood&MarrowTransplantn
state: Indiana
city: Baltimore
country: United States
facility: St. Agnes Hospital
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis University Cancer Center
state: Missouri
city: Portland
country: United States
facility: Northwest Cancer Specialists Salmon Creek Office
state: Oregon
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Dallas
country: United States
facility: Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Sugar Land
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
state: Texas
city: Brampton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Cortes JE, Lipton JH, Miller CB, Busque L, Akard LP, Pinilla-Ibarz J, Keir C, Warsi G, Lin FP, Mauro MJ. Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study. Clin Lymphoma Myeloma Leuk. 2016 May;16(5):286-96. doi: 10.1016/j.clml.2016.02.002. Epub 2016 Feb 16.