A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation

CML Clinical Trial

— ENESTgoal  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01744665
• Other study ID #: CAMN107AUS37
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2013
• Est. completion date: September 29, 2018

Study information

• Verified date: February 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5

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..

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: September 29, 2018
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• CML

Intervention

Drug:
• nilotinib
Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.

Locations

Country	Name	City	State
United States	Hendrick Cancer Center Hendricks Cancer Center	Abilene	Texas
United States	Billings Clinic Billings Clinic (8)	Billings Montana	Montana
United States	University of Alabama Comprehensive Cancer Center University of Alabama (8)	Birmingham	Alabama
United States	Rocky Mountain Cancer Centers USOR	Boulder	Colorado
United States	Montefiore Medical Center Montefiore Medicial Center	Bronx	New York
United States	University of Virginia	Charlottesville	Virginia
United States	Stroger Cook County Hospital Division of Hematology & Onc	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of South Carolina-Hollings Cancer Center Medical University of SC	Columbia	South Carolina
United States	Ohio State Comprehensive Cancer Center/James Cancer Hospital OSU Medical Center	Columbus	Ohio
United States	Texas Oncology P A Texas Oncology - Midland	Dallas	Texas
United States	Texas Oncology Texas Oncology - McAllen	Dallas	Texas
United States	Texas Oncology Texas Oncology - Plano West	Dallas	Texas
United States	City of Hope National Medical Center Dept of Oncology	Duarte	California
United States	Duke University Medical Center Duke University Med Ctr	Durham	North Carolina
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	Florida Cancer Specialists DeptofFloridaCancerSpecialists	Fort Myers	Florida
United States	Compassionate Care Research Group Inc CCCMG	Fountain Valley	California
United States	University of Texas Medical Branch SC	Galveston	Texas
United States	Banner MD Anderson Cancer Center Banner MD Anderson (2)	Gilbert	Arizona
United States	Hackensack University Medical Center John Theurer Cancer Center	Hackensack	New Jersey
United States	Carolina Oncology Specialists, PC	Hickory	North Carolina
United States	Oncology Consultants Oncology Consultants, P.A.	Houston	Texas
United States	The Methodist Hospital Cornell University	Houston	Texas
United States	University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Ct	Iowa City	Iowa
United States	University of Kansas Hospital and Medical Center Clinical Research Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology SC	Kennewick	Washington
United States	UC San Diego UC San Diego Cancer Ctr	La Jolla	California
United States	Michigan State University / Breslin Cancer Center Breslin Cancer Center (3)	Lansing	Michigan
United States	South Texas Cancer Center- McAllen	McAllen	Texas
United States	Medical College of Wisconsin Med College of WI	Milwaukee	Wisconsin
United States	West Virginia University/ Mary Babb Randolph Cancer Center Mary Babb Randolph Cancer Ctr	Morgantown	West Virginia
United States	Hematology Oncology Associates of Northern New Jersey PA Dept of Hem-Onc of Northern NJ	Morristown	New Jersey
United States	Wilshire Oncology Medical Group Corona Cancer Center	Multiple Locations	California
United States	Tennessee Oncology Dept. of Centennial Medical	Nashville	Tennessee
United States	Vanderbilt Univeristy Ingram Cancer Center (10)	Nashville	Tennessee
United States	Columbia University Medical Center Herbert Irving Pavilion	New York	New York
United States	Memorial Sloan Kettering Memorial Sloan Kettering (63)	New York	New York
United States	Weill Cornell Medical Center Dept. of Oncology	New York	New York
United States	MD Anderson Cancer Center - Orlando Cancer Center	Orlando	Florida
United States	Epic-Care	Pleasant Hill	California
United States	Northwest Cancer Specialists Compass Oncology -BKM	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Sutter Institute for Medical Research Oncology/Hematology	Sacramento	California
United States	University of Utah / Huntsman Cancer Institute Huntsman Cancer Center	Salt Lake City	Utah
United States	Brooke Army Medical Center Brooke Army Medical	San Antonio	Texas
United States	St Joseph Heritage Healthcare	Santa Rosa	California
United States	Scottsdale Healthcare/TGen Clinical Research Service SC	Scottsdale	Arizona
United States	Christus Schumpert Health System	Shreveport	Louisiana
United States	H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Ctr (67)	Tampa	Florida
United States	Westchester Medical Center NY Medical College	Valhalla	New York
United States	Waco Cancer and Research Center	Waco	Texas
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Wake Forest University Health Sciences Hematology and Oncology	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase	Percentage of particpants without confirmed loss of MMR within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase. Molecular relapse is defined as having a confirmed BCR-ABL ratio above MMR (2 consecutive BCR-ABL levels >0.1% IS taken approximately 4 weeks apart).	6 months after stopping nilotinib therapy
Secondary	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).	Relapse-free survival after the start of the TFR phase was summarized using the product-limit (Kaplan-Meier) estimates. The median for the relapse free survival and its 95% confidence intervals were provided. This analysis was performed on the FAS. Patients who dropped out without relapse were treated as censored observations.	7 years
Secondary	Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase	The percentage of participants without confirmed loss of MRR at 12 and 24 months is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12 and 24 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.	12 and 24 months after starting the TFR
Secondary	Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse	The percentage of participants who regained MR4.5 after restarting nilotinib will be calculated as the number of patients who achieved MR4.5 after having lost MR4 divided by the number of patients who lost MR4.	Restart of nilotinib up to month 6, 12 and 24
Secondary	Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.	Progression to AP/BC and death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC date.	Baseline up to approximately 5 years
Secondary	Overall Survival (OS)	OS was defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.	Baseline up to approximately 5 years
Secondary	Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment	The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) was used to assess the nature and impact of symptom burden on life. It consisted of 20 validated symptom items and 6 validated interference items. Each item was assessed on an 11 point scale with responses from 0-10, 0=not present and 10=as bad as you can imagine. Symptom score (SS) was calculated when a patient scored at least 8 items of the symptom items using the formula: (sum of scores for the items answered) / number of items answered. If a subject responded to < 8 symptom items, the score was considered missing. Interference score (IS) was calculated when a patient scored at least 4 items using the formula: (sum of scores for the items answered)/number of items answered. If a subject responded to < 4 interference items, the score was considered missing. The total symptom score was 0-200 and total interference score was 0-60. Mean change from baseline was summarized at all post-baseline time points	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
Secondary	Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set	The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state).	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
Secondary	Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set	The SF-8 questionnaire consisted of 8 items (general health, physical functioning, role physical, bodily pain, vitality, social functioning, role-emotional and mental health) and was used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item had a 1 to 5 or 1 to 6 point response range and the higher number in the raw scores indicated poorer quality of life. The physical and mental component summary measures were calculated using a norm-based scoring method given in the instrument guidelines. These norm-based scores were summarized at baseline and mean change from baseline for post-baseline time points. The norm-based scores (based on the US population) had a mean of 50 and standard deviation of 10. Higher norm-based summary scores indicated better health	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
Secondary	Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set	The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point	At month 3 in Consolidation Phase
Secondary	Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set	The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point	Month 12 in Consolidation Phase
Secondary	Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set	The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point	Month 24 in Consolidation Phase
Secondary	Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set	The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point	Month 6 in in Treatment Free Remission Phase
Secondary	Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set	The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point	Month 12 in in Treatment Free Remission Phase