Clinical Trials /

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

NCT03459534

Description:

In a multinational, multicenter, single-arm, open-label and Phase III Radotinib clinical study, chronic phase Ph+ chronic myeloid leukemia patients with failure 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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Phase 3 Study for the Efficacy and Safety of Radotinib in CP-CML Patients With Failure to Previous TKIs
  • Official Title: A Phase 3 Multinational, Multi-center, Single-arm, Open-label Study for the Efficacy and Safety of Radotinib in Chronic Phase Chronic Myeloid Leukemia Patients With Failure to Previous TKIs Therapy Including Imatinib

Clinical Trial IDs

  • ORG STUDY ID: RT51KRI03
  • NCT ID: NCT03459534

Conditions

  • Leukemia, Myeloid, Chronic Phase

Interventions

DrugSynonymsArms
RadotinibSUPECTRadotinib

Purpose

In a multinational, multicenter, single-arm, open-label and Phase III Radotinib clinical study, chronic phase Ph+ chronic myeloid leukemia patients with failure 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.

Trial Arms

NameTypeDescriptionInterventions
RadotinibExperimentalEnrolled 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.
  • Radotinib

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients aged 18 years old

          2. Chronic Phase Ph+ Chronic Myeloid Leukemia patients who failed 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)

               -  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 upper 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major Cytogenetic Response (MCyR)
Time Frame:at month 6
Safety Issue:
Description: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

Measure:Cytogenetic Response (CCyR)
Time Frame:at month 12/24, by month 24
Safety Issue:
Description: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.
Measure:Major molecular response
Time Frame:at month 12/24, by month 24
Safety Issue:
Description: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.
Measure:Overall Survival(OS)
Time Frame:by month 24
Safety Issue:
Description:OS is defined as the duration from the first day of Radotinib administration to the day of death for certain causes.
Measure:Progression Free Survival (PFS)
Time Frame:by month 24
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Il-Yang Pharm. Co., Ltd.

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