UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Multicenter Clinical Study on the Safety and Efficacy of Nilotinib Discontinuation in Patients with Chronic Myelogenous Leukemia-Chronic Phase and Complete Molecular Response
Title of the study (Brief title)	Stop Tasigna Trial (STAT2)
Region	Japan

Condition
Condition	Chronic Myelogenous Leukemia
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the safety and efficacy of nilotinib discontinuation in patients with chronic myelogenous leukemia in the chronic phase (CML-CP) who achieved a complete molecular response (CMR).
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	CMR rate at 1 year after discontinuation of nilotinib treatment in patients who have sustained CMR for 2 years after initiation of the study.
Key secondary outcomes	1) CMR rate at 2 and 3 years after discontinuation of nilotinib treatment in patients who have sustained CMR for 2 years after initiation of the study. Recurrence-free survival (RFS), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) at 1, 2, and 3 years after the discontinuation of nilotinib. 2) Rate of patients who have sustained CMR for 2 years at 24 months after initiation of the study. 3) Correlation between the time to CMR/MMR and the CMR rate at 1, 2, and 3 years after the discontinuation of treatment. 4) Correlation between the CMR duration prior to the discontinuation of nilotinib treatment and the CMR rate at 1, 2, and 3 years after discontinuation. 5) Exploration of predictors of CMR sustenance during nilotinib treatment.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	2 capsules (150 mg) of nilotinib will be taken twice daily (600 mg/day) for 2 years. Patients who sustain CMR for 2 years following 2 years of treatment then discontinue the study medication and are carefully followed up for another 3 years.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	16 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Patients who have never had blast crisis or accelerated CML. 2) Patients with confirmed CMR based on the result of an assay conducted within 1 year prior to registration 3) Age 16 years or older. 4) Patients with an ECOG performance status of 0-2. 5) Patients who have the following clinical laboratory values: i) Serum bilirubin (T.Bil) <=1.5 X the upper limit of normal for the clinical study site (ULN) ii) AST and ALT <=2.5 X ULN iii) Alkaline phosphatase (ALP) <=2.5 X ULN iv) Serum creatinine (s-Cr) <=3.0 X ULN v) Serum lipase <=1.5 X ULN vi) Potassium (K) >=the lower limit of normal at the clinical study site (LLN) vii) Magnesium (Mg) >= LLN viii) Phosphate (IP) >= LLN ix) Total calcium (Ca) (after adjustment by serum albumin) >= LLN x) QTc <450 msec on ECG 6) Patients who can attend the clinical study site in accordance with the pre-defined schedule. 7) Written informed consent from the subject (from the legal representative if the subject is under 20 years old).
Key exclusion criteria	1) Patients who are participating in any other clinical trial. 2) Patients with the T315I point mutation of BCR-ABL. 3) Patients with a history of hematopoietic stem cell transplantation. 4) Patients with one of the following indicators of cardiovascular dysfunction. i) The QT interval cannot be measured on the ECG ii) Complete left bundle branch block iii) Ventricular pacemaker iv) Congenital QT interval prolongation syndrome or a family history of QT interval prolongation syndrome v) History of or current severe ventricular or atrial tachycardia vi) Clinically significant bradycardia at rest (<50 bpm) vii) History of clinically diagnosed myocardial infarction viii) History of unstable angina within 12 months prior to initiation of the study ix) Other clinically significant cardiovascular complications 5) Patients with another primary malignant tumor. 6) Gastrointestinal dysfunction or diseases that could greatly influence absorption of the study medication. 7) Patients with a history of acute or chronic pancreatitis within 1 year prior to participation to the study. 8) Pregnant women or those with suspected pregnancy. Nursing women and those who plan to become pregnant during the study period. 9) Patients with multiple invasive cancers within 5 years prior to initiation of the study. 10) Patients with other serious or uncontrollable complications. 11) Patients with a psychiatric illness or symptoms that make it difficult to participate in the study. 12) Patients with cognitive dysfunction. 13) Other patients whom the investigator considers to be unsuitable for participation in the study.
Target sample size	100

Research contact person
Name of lead principal investigator	Naoto Takahashi
Organization	Akita University School of Medicine
Division name	Department of Hematology, Nephrology and Rheumatology
Address	1-1-1 Hondo, Akita, 010-8543, Japan
TEL	018-884-6115
Email	naotot@doc.med.akita-u.ac.jp

Public contact
Name of contact person	Naoto TAKAHASHI
Organization	Akita University School of Medicine
Division name	Department of Hematology, Nephrology and Rheumatology
Address	1-1-1 Hondo, Akita, 010-8543, Japan
TEL	018-884-6115
Homepage URL
Email	naotot@doc.med.akita-u.ac.jp

Sponsor
Institute	Akita university and the NPO Tohoku Hematology Expert Meeting
Institute
Department

Funding Source
Organization	Novartis Pharma K.K.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2011 Year 07 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2011 Year 05 Month 31 Day
Anticipated trial start date	2011 Year 07 Month 01 Day
Last follow-up date	2018 Year 03 Month 01 Day
Date of closure to data entry	2018 Year 03 Month 15 Day
Date trial data considered complete	2018 Year 03 Month 15 Day
Date analysis concluded	2018 Year 03 Month 31 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	http://www.haematologica.org/content/haematol/103/11/1835.full.pdf
Results	We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achiev- ing a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free sur- vival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor- withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib.
Other related information

Management information
Registered date	2011 Year 07 Month 01 Day
Last modified on	2018 Year 11 Month 07 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000006983