UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000002201 |
|---|---|
| Receipt number | 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 15:21:21 |
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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
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
naotot@doc.med.akita-u.ac.jp
Sponsor or person
Institute
East Japan CML Study Group (EJCML)
Institute
Department
Personal name
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
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
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002705
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