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UMIN ID:

Recruitment status Completed
Unique ID issued by UMIN UMIN000002201
Receipt No. R000002705
Scientific Title Prospective multicenter clinical study evaluating efficacy and safety of Nilotinib in Ph chromosome-positive (Ph+) CML patients with Imatinib resistance or intolerance
Date of disclosure of the study information 2009/07/15
Last modified on 2018/11/07

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Basic information
Public title Prospective multicenter clinical study evaluating efficacy and safety of Nilotinib in Ph chromosome-positive (Ph+) CML patients with Imatinib resistance or intolerance
Acronym Prospective multicenter clinical study of Nilotinib in CML patients with Imatinib resistance or intolerance
Scientific Title Prospective multicenter clinical study evaluating efficacy and safety of Nilotinib in Ph chromosome-positive (Ph+) CML patients with Imatinib resistance or intolerance
Scientific Title:Acronym Prospective multicenter clinical study of Nilotinib in CML patients with Imatinib resistance or intolerance
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 assess the efficacy and safety of Nilotinib in Ph chromosome-positive (Ph+) CML patients with Imatinib resistance or intolerance.
Basic objectives2 Safety,Efficacy
Basic objectives -Others
Trial characteristics_1 Confirmatory
Trial characteristics_2
Developmental phase Phase II

Assessment
Primary outcomes To assess the efficacy of twice daily administration of Nilotinib at a dose of 400 mg in Ph chromosome-positive (Ph+) CML patients with Imatinib resistance or intolerance based on the rate of major molecular response at 12 months after starting treatment.
Key secondary outcomes 1) To assess the rate of complete cytogenetic response (CCyR) at 12 months.
2) To assess the times to achieve a CCyR and a major molecular response (MMR) every 3 months.
3) To assess durations of MMR every 3 months.
4) To assess the progression-free survival (PFS), the event-free survival (EFS), and the overall survival (OS) at 5 years.
5) To assess the actual dose intensity at 12 months in the groups which have achieved a CCyR or a MMR and the groups which have not achieved a CCyR or a MMR.
6) To assess patient profiles such as BCR-ABL point mutations and the blood levels of Imatinib before Nilotinib treatment.
7) To assess profiles of BCR-ABL point mutations at 12 months in the groups which have achieved a CCyR and a MMR and in the groups which have not achieved a CCyR and a MMR.
8) To assess the safety of twice daily administration of Nilotinib 400 mg dosage.

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 Nilotinib will be administered twice daily at a dose of 400 mg (800 mg/day) for 1 year.
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
20 years-old <=
Age-upper limit
80 years-old >
Gender Male and Female
Key inclusion criteria 1) Patient who has the Philadelphia chromosome confirmed by chromosome analysis at the first visit.
2) Patient who has not experienced a blast phase of CML before treatment with Nilotinib.
3) Chronic or accelerate phase CML patients who has been treated with Imatinib for 18 months or longer and diagnosed with Imatinib resistance or intolerance.
4) Patient with the ECOG performance status of 0, 1 or 2.
6) Patient who meets the following criteria for laboratory tests.
(1) T.Bill < 1.5 X ULN
(2) AST and ALT < 2.5 X ULN
(3) ALP < 2.5 X ULN
(4) Cre 1.5 < 1.5 X ULN
(5) AMY and Lipase < 1.5 X ULN
(6) K > LLN
(7) Mg > LLN
(8) IP > LLN
(9) Corrected Ca > LLN
(10) LVEF>45% or LLN by echocardiography
(11) QTc<450 msec by electrocardiography
6) Patient from whom an informed consent for the clinical study has been obtained.
Key exclusion criteria 1) Patient who exhibits the T315I BCR-ABL mutation.
2) Patient who is pregnant or breastfeeding.
3) Patient does not agree to use contraceptive methods to prevent pregnancy.
4) Patient who has any cardiac disturbances including the following conditions.
(1) Unmeasurable QT interval by ECG
(2) Complete left bundle branch block
(3) Use of a ventricular pacemaker
(4) Congenital long QT syndrome or family history of long QT syndrome
(5) History or complication of serious ventricular or atrial tachycardia
(6) Clinically serious resting bradycardia(<50 bpm)
(7) History of clinically diagnosed myocardial infarction
(8) History of unstable angina within 12 months before start of study
(9) Other clinically important heart diseases
5) Patient who has a history of non-adherence to medications or patient from whom an informed consent can not be obtained.
6) Patient who has any gastrointestinal disorders or diseases which may affect the absorption of the study drug.
7) Patients who has acute or chronic hepatic disease, pancreatic disease, or severe renal disease unrelated to the primary disease.
Target sample size 40

Research contact person
Name of lead principal investigator
1st name
Middle name
Last name Kenichi Sawada
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 018-884-6111
Email ksawada@doc.med.akita-u.ac.jp

Public contact
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 018-834-1111
Homepage URL
Email naotot@doc.med.akita-u.ac.jp

Sponsor
Institute East Japan CML Study Group (EJCML)
Institute
Department

Funding Source
Organization NPO Ibaraki hematology, Oncology & Palliative Expert Meeting (IB-HOPE)
Organization
Division
Category of Funding Organization Non profit foundation
Nationality of Funding Organization Japan

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

IRB Contact (For public release)
Organization
Address
Tel
Email

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
2009 Year 07 Month 15 Day

Related information
URL releasing protocol
Publication of results Published

Result
URL related to results and publications http://www.biomarkerres.org/content/2/1/6
Number of participants that the trial has enrolled
Results
We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily. The major molecular response (MMR) rate was 47.8% at 12 months among 35 patients who did not demonstrate an MMR at study entry. Somatic BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35-bp insertion [35INS]) were detected in 3 patients at 12 months or upon discontinuation of nilotinib. Although 75.5% of patients were still being treated at 12 months, nilotinib treatment was discontinued because of progressing disease in 1 patient, insufficient effect in 2, and adverse events in 9. There was no statistically significant correlation between MMR and trough concentrations of nilotinib. Similarly, no correlation was observed between trough concentrations and adverse events, except for pruritus and hypokalemia. Hyperbilirubinemia was frequently observed (all grades, 51.0%; grades 2-4, 29%; grades 3-4, 4.1%). Hyperbilirubinemia higher than grade 2 was significantly associated with the uridine diphosphate glucuronosyltransferase (UGT)1A9 I399C/C genotype (P=0.0086; Odds Ratio, 21.2; 95% Confidence Interval 2.2-208.0). 
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

Progress
Recruitment status Completed
Date of protocol fixation
2009 Year 03 Month 01 Day
Date of IRB
Anticipated trial start date
2009 Year 03 Month 06 Day
Last follow-up date
2012 Year 03 Month 01 Day
Date of closure to data entry
2012 Year 09 Month 01 Day
Date trial data considered complete
2012 Year 12 Month 01 Day
Date analysis concluded
2013 Year 03 Month 01 Day

Other
Other related information

Management information
Registered date
2009 Year 07 Month 14 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/ctr_e/ctr_view.cgi?recptno=R000002705

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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