Clinical trial NCT01744665: A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation
Official title: A Phase II Randomized, Multicenter Study of Treatment-free Remission in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Patients Who Achieve and Sustain MR4.5 After Switching to Nilotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CML
Keywords: CML, chronic myeloid leukemia, stop, niotinib, discontinue, imatinib, switch, MR4.5, undetectable, bcr-abl
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-12-07
Enrollment: 59
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: To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5

Detailed description: Study protocol included criteria for study termination that was met when \> 2 patients lost CCyR during TFR phase (\> 1% BCR-ABL); This study was terminated early as \> 2 cases of confirmed loss of complete cytogenetic response were reported despite BCR-ABL monitoring during the TFR Phase. All cases achieved MR4.5 after Nilotinib treatment re-initiation and maintained until end of study; trial did not mandate re-initiation within 4 weeks after loss of MMR_ that was a requirement in other Nilotinib TFR trials Initial sample size was 300 patients with CML-CP; Amendment #2 in June 2015 reduced sample size to 59 due to recruitment challenges; Study endpoint analysis and interpretations of data were challenging due to small sample size for early study closure..

Eligibility criteria: Inclusion Criteria:

* diagnosis of CML
* Treated with at least 1 year of imatinib
* Bcr-Abl level by PCR must be less than or equal to 0.1% and greater than 0.0032% by PCR reported on the International scale confirmed during screening
* Written informed consent obtained prior to any screening procedures performed

Exclusion Criteria:

* T315I mutation
* Prior imatinib failure or had accelerated phase or blast crisis CML
* Impaired cardiac function
* Pregnant or lactating women

Primary outcomes:
measure: Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase
timeFrame: 6 months after stopping nilotinib therapy
Secondary outcomes:
measure: Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5).
timeFrame: 7 years
measure: Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase
timeFrame: 12 and 24 months after starting the TFR
measure: Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse
timeFrame: Restart of nilotinib up to month 6, 12 and 24
measure: Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.
timeFrame: Baseline up to approximately 5 years
measure: Overall Survival (OS)
timeFrame: Baseline up to approximately 5 years
measure: Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment
timeFrame: From baseline to time to when MR4.5 is confirmed, up to 24 months, and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
measure: Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set
timeFrame: From baseline to time to when MR4.5, up to 24 months, is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
measure: Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set
timeFrame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
measure: Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set
timeFrame: At month 3 in Consolidation Phase
measure: Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set
timeFrame: Month 12 in Consolidation Phase
measure: Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set
timeFrame: Month 24 in Consolidation Phase
measure: Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set
timeFrame: Month 6 in in Treatment Free Remission Phase
measure: Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set
timeFrame: Month 12 in in Treatment Free Remission Phase
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center University of Alabama (8)
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center Banner MD Anderson (2)
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare/TGen Clinical Research Service SC
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center Dept of Oncology
state: California
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group Inc CCCMG
state: California
city: La Jolla
country: United States
facility: UC San Diego UC San Diego Cancer Ctr
state: California
city: Multiple Locations
country: United States
facility: Wilshire Oncology Medical Group Corona Cancer Center
state: California
city: Pleasant Hill
country: United States
facility: Epic-Care
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research Oncology/Hematology
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers USOR
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists DeptofFloridaCancerSpecialists
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center - Orlando Cancer Center
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Ctr (67)
state: Florida
city: Chicago
country: United States
facility: Stroger Cook County Hospital Division of Hematology & Onc
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Ct
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Hospital and Medical Center Clinical Research Center
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Shreveport
country: United States
facility: Christus Schumpert Health System
state: Louisiana
city: Lansing
country: United States
facility: Michigan State University / Breslin Cancer Center Breslin Cancer Center (3)
state: Michigan
city: Billings Montana
country: United States
facility: Billings Clinic Billings Clinic (8)
state: Montana
city: Hackensack
country: United States
facility: Hackensack University Medical Center John Theurer Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Hematology Oncology Associates of Northern New Jersey PA Dept of Hem-Onc of Northern NJ
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center Montefiore Medicial Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Memorial Sloan Kettering (63)
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center Dept. of Oncology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center Herbert Irving Pavilion
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center NY Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center Duke University Med Ctr
state: North Carolina
city: Hickory
country: United States
facility: Carolina Oncology Specialists, PC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences Hematology and Oncology
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Comprehensive Cancer Center/James Cancer Hospital OSU Medical Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists Compass Oncology -BKM
state: Oregon
city: Columbia
country: United States
facility: University of South Carolina-Hollings Cancer Center Medical University of SC
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology Dept. of Centennial Medical
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univeristy Ingram Cancer Center (10)
state: Tennessee
city: Abilene
country: United States
facility: Hendrick Cancer Center Hendricks Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - McAllen
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Plano West
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P A Texas Oncology - Midland
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch SC
state: Texas
city: Houston
country: United States
facility: Oncology Consultants Oncology Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Cornell University
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center- McAllen
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center Brooke Army Medical
state: Texas
city: Waco
country: United States
facility: Waco Cancer and Research Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman Cancer Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology SC
state: Washington
city: Morgantown
country: United States
facility: West Virginia University/ Mary Babb Randolph Cancer Center Mary Babb Randolph Cancer Ctr
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Med College of WI
state: Wisconsin
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: