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

Sponsor
Il-Yang Pharm. Co., Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03459534
Collaborator
(none)
173
18
1
81.2
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Radotinib HCl
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
173 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Multinational, Multi-center, Single-arm, Open-label Study for the Efficacy and Safety of Radotinib in Ph+ Chronic Phase Chronic Myeloid Leukemia Patients With Failure or Intolerance to Previous TKIs Therapy Including Imatinib
Actual Study Start Date :
Jun 25, 2018
Anticipated Primary Completion Date :
Jan 29, 2025
Anticipated Study Completion Date :
Apr 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

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

    Primary Outcome Measures

    1. Major Cytogenetic Response (MCyR) [at month 6]

      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.

    Secondary Outcome Measures

    1. Cytogenetic Response (CCyR) [at month 12/24, by month 24]

      CCyR is defined as complete loss of Ph chromosome based on ≥20 metaphase myelocytes. Chromosome test results from <20 metaphase myelocytes will be excluded from the analysis.

    2. Major molecular response [at month 12/24, by month 24]

      MMR is defined as a ≥3-log reduction in BCR-ABL1 transcript level from the standardized reference or BCR-ABL1/ABL % of ≤0.1% according to the international reference when the level of BCR-ABL1 gene was measured by RQ-PCR, a standardized quantitative genetic method.

    3. Overall Survival(OS) [by month 24]

      OS is defined as the duration from the first day of Radotinib administration to the day of death for certain causes.

    4. Progression Free Survival (PFS) [by month 24]

      PFS is defined as the duration from the first day of Radotinib administration to the earliest day of disease progression or death for certain causes.

    Other Outcome Measures

    1. BCR-ABL1 point mutation [up to month 24]

      Incidence rate of BCR-ABL1 point mutations that are newly found during the course of radotinib treatment

    2. correlation between the concentration of radotinib in blood and the response (efficacy and safety) [up to month 24]

      To measure the concentration of radotinib in blood

    3. Incidence of Radotinib-Adverse Events [up to month 24]

      Toxicities will be evaluated in all subjects treated with radotinib.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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)

    1. Women of childbearing potential should have a negative serum or urine pregnancy test within 14 days of the enrollment.

    2. 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

    1. Patients with T315I point mutations

    2. Patients with central nervous system involvement as cytopathologically confirmed

    3. Severe or uncontrolled chronic disease

    4. Significant medical history of congenital or acquired bleeding disorders that are not related to leukemia

    5. Patients who previously received radiotherapy to at least 25% of the bodies with high portion of bone marrow

    6. 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.

    7. Patients who participated in other clinical study and are receiving any other IP.

    8. Patients who cannot give consent to the clinical study.

    9. Patients who have concurrently clinically significant primary malignancy

    10. 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.

    11. 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.

    12. Gastrointestinal disorder or gastrointestinal disease that may result in a significant change in the absorption of the investigational product

    13. Medical history of acute or chronic pancreatitis within the past one year

    14. Acute or chronic liver, pancreas, or severe kidney disease that are not associated with the disease

    15. 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.

    16. 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

    1. Men patients who are unwilling to use and appropriate method of contraception during the study

    2. Patients who have hypersensitivity to active ingredient or any of the excipients of this investigational product

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Uijeongbu Eulji Medical Center, Eulji University Uijeongbu-si Gyeonggi-do Korea, Republic of 11749
    2 Territorial State Budgetary Institution Barnaul Russian Federation 656024
    3 Federal State Budgetary Institution of Science Kirov Russian Federation 610027
    4 Federal State Budgetary Institution Moscow Russian Federation 125167
    5 Hematology Centre based on City Clin. Hosp. n.a. S.P. Botkin Moscow Russian Federation 300186883
    6 Federal State Budgetary Institution Saint-Petersburg Russian Federation 191024
    7 Federal State Budgetary Institution Saint-Petersburg Russian Federation 197341
    8 Ankara University Medical Faculty Ankara Turkey
    9 Gazi University Medical Faculty Ankara Turkey
    10 Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty Istanbul Turkey
    11 Ege University Medical Faculty Izmir Turkey
    12 Mersin University Medical Faculty Mersin Turkey
    13 Ondokuz Mayis Univ. Med. Fac. Samsun Turkey
    14 CI Cherkasy Regional Oncological Dispensary of CRC Cherkassy Ukraine
    15 CTPI Chernihiv Regional Oncological Dispensary Chernihiv Ukraine
    16 CI Dnipropetrovsk CMCH #4 OF Dnipropetrovsk RC Dnipro Ukraine
    17 Institute of CR of SI NSC of Radiation Medicine of NAMSU H&T Unit Kyiv Ukraine
    18 SI Institute of Blood Pathology and Transfusion Medicine of AMSU Lviv Ukraine

    Sponsors and Collaborators

    • Il-Yang Pharm. Co., Ltd.

    Investigators

    • Principal Investigator: Dong Wook Kim, the Catholic University of Korea's St. Mary's Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Il-Yang Pharm. Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT03459534
    Other Study ID Numbers:
    • RT51KRI03
    • 2018-003810-42
    First Posted:
    Mar 9, 2018
    Last Update Posted:
    Jan 4, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 4, 2022