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

NCT03459534 | Recruiting Phase 3

• 2 other identifiers: RT51KRI032018-003810-42
• Study Type: interventional
• Target: 173
• Locations: 4 countries
• Sites: 18

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Major Cytogenetic Response (MCyR)

  MCyR is defined as 0\~35% CCyR+PCyR based on ≥20 metaphase myelocytes. Chromosome test results from \<20 metaphase myelocytes will be excluded from the analysis.

  at month 6

Secondary Outcomes (4)

• Cytogenetic Response (CCyR)

  at month 12/24, by month 24

• Major molecular response

  at month 12/24, by month 24

• Overall Survival(OS)

  by month 24

• Progression Free Survival (PFS)

  by month 24

Other Outcomes (3)

• BCR-ABL1 point mutation

  up to month 24

• correlation between the concentration of radotinib in blood and the response (efficacy and safety)

  up to month 24

• Incidence of Radotinib-Adverse Events

  up to month 24

Study Arms (1)

Radotinib HCl

EXPERIMENTAL

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.

Drug: Radotinib HCl

Interventions

Radotinib HCl 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.

Also known as: SUPECT

Radotinib HCl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 years old
• Chronic Phase Ph+ Chronic Myeloid Leukemia patients who failed or intolerance the previous TKIs therapy including Imatinib Imatinib
• ECOG scale 0, 1 or 2
• 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
• 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)

You may not qualify if:

• Patients who have been diagonised accelerated phase and blast crisis CML in previous therapy if only once.
• Patients with CCyR at the time of screening
• 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

Sponsors & Collaborators

• Il-Yang Pharm. Co., Ltd.: lead

Study Sites (18)

Territorial State Budgetary Institution

Barnaul, 656024, Russia

NOT YET RECRUITING

Federal State Budgetary Institution of Science

Kirov, 610027, Russia

RECRUITING

Federal State Budgetary Institution

Moscow, 125167, Russia

NOT YET RECRUITING

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

Moscow, 300186883, Russia

RECRUITING

Federal State Budgetary Institution

Saint Petersburg, 191024, Russia

RECRUITING

Federal State Budgetary Institution

Saint Petersburg, 197341, Russia

RECRUITING

Uijeongbu Eulji Medical Center, Eulji University

Uijeongbu-si, Gyeonggi-do, 11749, South Korea

RECRUITING

Ankara University Medical Faculty

Ankara, Turkey (Türkiye)

RECRUITING

Gazi University Medical Faculty

Ankara, Turkey (Türkiye)

RECRUITING

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, Turkey (Türkiye)

RECRUITING

Ege University Medical Faculty

Izmir, Turkey (Türkiye)

RECRUITING

Mersin University Medical Faculty

Mersin, Turkey (Türkiye)

RECRUITING

Ondokuz Mayis Univ. Med. Fac.

Samsun, Turkey (Türkiye)

RECRUITING

CI Cherkasy Regional Oncological Dispensary of CRC

Cherkassy, Ukraine

RECRUITING

CTPI Chernihiv Regional Oncological Dispensary

Chernihiv, Ukraine

RECRUITING

CI Dnipropetrovsk CMCH #4 OF Dnipropetrovsk RC

Dnipro, Ukraine

RECRUITING

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

Kyiv, Ukraine

RECRUITING

SI Institute of Blood Pathology and Transfusion Medicine of AMSU

Lviv, Ukraine

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dong Wook Kim

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Na Yun Kim

CONTACT

+82.70.7165.7316; nykim@ilyang.co.kr

Kang Hi An

CONTACT

+82.70.7165.7322; khan@ilyang.co.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: March 9, 2018
• Study Start: June 25, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 28, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6); KR (1); UA (5); TU (6)