A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure or Intolerance to Previous TKIs

NCT ID: NCT03459534

Last Updated: 2024-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-25

Study Completion Date

2027-12-31

Brief Summary

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In a multinational, multicenter, single-arm, open-label and Phase III Radotinib clinical study, chronic phase Ph+ chronic myeloid leukemia patients with failure or intolerance to previous TKIs therapy including Imatinib will be recruited. In this phase 3 study, 173 subjects are expected to be enrolled in a single arm with the administration of Radotinib 400mg twice daily, which includes 10% of dropout rate.

Detailed Description

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Conditions

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Chronic Myeloid Leukemia, Chronic Phase CML, Chronic Phase CML, Refractory CML - Philadelphia Chromosome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radotinib HCl

Enrolled subjects will continue to administer Radotinib 400mg twice daily (800mg/day) orally every 12 hours at regular dosing hours for 12 months.

Dose modification is allowed if the subject cannot comply with the protocol-defined dosing schedule due to hematologic or non-hematologic toxicities and toxicities resolve within 28 days (within 42 days for hematologic toxicities). For radotinib, maximum 2 dose reductions will be allowed by stage to 600mg and to 400mg.

Group Type EXPERIMENTAL

Radotinib HCl

Intervention Type DRUG

1. Brand name/manufacturer: Supect Cap./IL-YANG PHARM. Co., Ltd.
2. Active ingredient: radotinib HCl 106.8mg (100mg as radotinib) or HCl 213.6mg (200mg as radotinib)
3. Appearance and formulation: hard capsule with a light blue cap and a body containing pale yellow powder
4. Storage conditions: Store in an airtight light proof container at room temperature.

Interventions

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Radotinib HCl

1. Brand name/manufacturer: Supect Cap./IL-YANG PHARM. Co., Ltd.
2. Active ingredient: radotinib HCl 106.8mg (100mg as radotinib) or HCl 213.6mg (200mg as radotinib)
3. Appearance and formulation: hard capsule with a light blue cap and a body containing pale yellow powder
4. Storage conditions: Store in an airtight light proof container at room temperature.

Intervention Type DRUG

Other Intervention Names

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SUPECT

Eligibility Criteria

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Inclusion Criteria

1. Male or female patients aged 18 years old
2. Chronic Phase Ph+ Chronic Myeloid Leukemia patients who failed or intolerance the previous TKIs therapy including Imatinib Imatinib
3. ECOG scale 0, 1 or 2
4. Chronic phase is defined as all of the following conditions that subjects meet.

* Blast in peripheral blood and bone marrow \<15%
* The sum of blast and promyelocyte in peripheral blood and bone marrow \<30%
* Basophil in peripheral blood \<20%
* Platelets count ≥50 × 10\^9/L (≥ 50,000/mm3) (But, transient prior therapy related thrombocytopenia \[\< 50 × 109/L (\< 50,000/mm3)\] is acceptable
* No evidence of involvement of extramedullary leukemia other than enlargements of liver and spleen
5. Patients who have adequate organ functions as defined below:

* Total bilirubin \< 1.5 × upper limit of normal (ULN)
* SGOT and SGPT \< 2.5× ULN
* Creatinine \< 1.5 × ULN
* Serum amylase and lipase ≤ 1.5 × ULN
* Alkaline Phosphatase ≤ 2.5 × ULN (only if not related to the tumor)
6. Women of childbearing potential should have a negative serum or urine pregnancy test within 14 days of the enrollment.
7. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month (4 weeks) after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria

1. Patients who have been diagonised accelerated phase and blast crisis CML in previous therapy if only once.
2. Patients with CCyR at the time of screening
3. Any below impaired cardiac function:

* LVEF \<45% or \< lower bound of normal limit of study site (whichever higher), confirmed by echocardiogram at the site
* Patients who cannot have QT intervals measured according to ECG
* Complete left bundle branch block
* Patients with cardiac pacemakers
* Patients with congenital long QT syndrome or the family history of known long QT syndrome
* History of, or presence of symptomatic ventricular or atrial tachyarrhythmias
* Clinically significant resting bradycardia (\< 50 bpm)
* The mean QTcF \>450msec following three consecutive ECG tests at baseline

: Screening test will be performed again for QTcF after the adjustment of electrolyte if QTcF \>450msec and the electrolyte is not within the normal range.
* Medical history of clinically confirmed myocardial infarction
* Medical history of unstable angina (within last 12 months)
* Other clinically significant cardiac disease
4. Patients with T315I point mutations
5. Patients with central nervous system involvement as cytopathologically confirmed
6. Severe or uncontrolled chronic disease
7. Significant medical history of congenital or acquired bleeding disorders that are not related to leukemia
8. Patients who previously received radiotherapy to at least 25% of the bodies with high portion of bone marrow
9. Patients who received the major surgery within 4 weeks before the initiation of the IP administration or who failed to recover from the surgery that was performed before then.
10. Patients who participated in other clinical study and are receiving any other IP.
11. Patients who cannot give consent to the clinical study.
12. Patients who have concurrently clinically significant primary malignancy
13. Patients currently receiving treatment with a strong CYP3A4 inhibitors or strong CYP3A4 inducers or therapeutic Cumarin derivatives and that can neither stop the administration of these drugs before the start of the IP administration nor switch to other drugs.
14. Patients who are currently receiving treatment with a medication that has the potential to prolong QT intervals and can neither stop the administration of the drugs before the start of the IP administration nor switch to other drugs. If subjects need to start such drug treatments during the study, they should contact the sponsor, IL-YANG PHARM. Co., Ltd.
15. Gastrointestinal disorder or gastrointestinal disease that may result in a significant change in the absorption of the investigational product
16. Medical history of acute or chronic pancreatitis within the past one year
17. Acute or chronic liver, pancreas, or severe kidney disease that are not associated with the disease
18. Patients known seropositive to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, or cirrhosis. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA \< 500 IU/mL or site specific local lab normal range lower limit assessed by investigator), and cured hepatitis C patients can be enrolled.
19. Women patients that meet the following conditions should be excluded from the clinical study.

* Pregnancy
* Breastfeeding
* Pregnancy confirmed at screening pregnancy test
* Women of childbearing potential who is unwilling to use an appropriate method of contraception during the study
20. Men patients who are unwilling to use and appropriate method of contraception during the study
21. Patients who have hypersensitivity to active ingredient or any of the excipients of this investigational product
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Il-Yang Pharm. Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dong Wook Kim

Role: PRINCIPAL_INVESTIGATOR

the Catholic University of Korea's St. Mary's Hospital

Locations

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Territorial State Budgetary Institution

Barnaul, , Russia

Site Status NOT_YET_RECRUITING

Federal State Budgetary Institution of Science

Kirov, , Russia

Site Status RECRUITING

Federal State Budgetary Institution

Moscow, , Russia

Site Status NOT_YET_RECRUITING

Hematology Centre based on City Clin. Hosp. n.a. S.P. Botkin

Moscow, , Russia

Site Status RECRUITING

Federal State Budgetary Institution

Saint Petersburg, , Russia

Site Status RECRUITING

Federal State Budgetary Institution

Saint Petersburg, , Russia

Site Status RECRUITING

Uijeongbu Eulji Medical Center, Eulji University

Uijeongbu-si, Gyeonggi-do, South Korea

Site Status RECRUITING

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Site Status RECRUITING

Mersin University Medical Faculty

Mersin, , Turkey (Türkiye)

Site Status RECRUITING

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Site Status RECRUITING

CI Cherkasy Regional Oncological Dispensary of CRC

Cherkassy, , Ukraine

Site Status RECRUITING

CTPI Chernihiv Regional Oncological Dispensary

Chernihiv, , Ukraine

Site Status RECRUITING

CI Dnipropetrovsk CMCH #4 OF Dnipropetrovsk RC

Dnipro, , Ukraine

Site Status RECRUITING

Institute of CR of SI NSC of Radiation Medicine of NAMSU H&T Unit

Kyiv, , Ukraine

Site Status RECRUITING

SI Institute of Blood Pathology and Transfusion Medicine of AMSU

Lviv, , Ukraine

Site Status RECRUITING

Countries

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Russia South Korea Turkey (Türkiye) Ukraine

Central Contacts

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Na Yun Kim

Role: CONTACT

+82.70.7165.7316

Kang Hi An

Role: CONTACT

+82.70.7165.7322

Facility Contacts

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Dong-Wook Kim, MD

Role: primary

Other Identifiers

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2018-003810-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RT51KRI03

Identifier Type: -

Identifier Source: org_study_id

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