UMIN-CTR Clinical Trial

Public title

Multicenter Clinical Study on the Safety and Efficacy of Nilotinib Discontinuation in Patients with Chronic Myelogenous Leukemia-Chronic Phase and Complete Molecular Response

Acronym

Stop Tasigna Trial (STAT2)

Scientific Title

Multicenter Clinical Study on the Safety and Efficacy of Nilotinib Discontinuation in Patients with Chronic Myelogenous Leukemia-Chronic Phase and Complete Molecular Response

Scientific Title:Acronym

Stop Tasigna Trial (STAT2)

Region

Japan

Condition

Chronic Myelogenous Leukemia

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

YES

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

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.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Naoto Takahashi

Organization

Akita University School of Medicine

Division name

Department of Hematology, Nephrology and Rheumatology

Zip code

Address

1-1-1 Hondo, Akita, 010-8543, Japan

TEL

018-884-6115

Email

naotot@doc.med.akita-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Naoto TAKAHASHI

Organization

Akita University School of Medicine

Division name

Department of Hematology, Nephrology and Rheumatology

Zip code

Address

1-1-1 Hondo, Akita, 010-8543, Japan

TEL

018-884-6115

Homepage URL

Email

naotot@doc.med.akita-u.ac.jp

Institute

Akita university and the NPO Tohoku Hematology Expert Meeting

Institute

Department

Personal name

Organization

Novartis Pharma K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2011

Year

07

Month

01

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://www.haematologica.org/content/haematol/103/11/1835.full.pdf

Number of participants that the trial has enrolled

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.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2011

Year

05

Month

31

Day

Date of IRB

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

Other related information

Registered date

2011

Year

07

Month

01

Day

Last modified on

2018

Year

11

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006983