Efficacy and Safety of Dose Redution of Radotinib as a First Line Treament in Ph+ CML

A Single-arm, Open-label, Multicenter, Investigator-led Observational Study to Evaluate the Efficacy and Safety of Dose Reduction of Radotinib as a First-line Treatment in Patients With Newly Diagnosed Chronic Phase Ph+ Chronic Myeloid Leukemia.

The goal of this observational study is to learn about the efficacy and safety profile when Radotinib dose redution is performed in Ph+ CML subjects.

The main efficacy is checked by MMR rate by 12 months from IP treatment.

Study Overview

• Status: Recruiting
• Conditions: Chronic Phase Ph+ Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: Radotinib Hydrochloride

• Study Type: Observational
• Enrollment (Estimated): 168

Contacts and Locations

• Study Contact: Name: Na Yun Kim; Phone Number: 82-70-7165-7316; Email: nykim@ilyang.co.kr

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Not yet recruiting
    • Keimyung University Daegu Dongsan Hospital
    • Contact: Young Rok Do; Phone Number: 82-70-7165-7316; Email: dyr1160@dsmc.or.kr
  • Gyeonnggi-do
    • Anyang-si, Gyeonnggi-do, Korea, Republic of, 14068
      • Recruiting
      • Hallym University Sacred Heart Hosptial
      • Contact: Dae Young Jang; Phone Number: 82-70-7165-7316; Email: fhdzang@hallym.or.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Newly diagnosed, CP-CML patients

Description

Inclusion Criteria:

1. Male or female patients aged 19 years old or older

2. Patients with confirmed diagnosis of chronic phase CML within last 8weeks(throung chromosome testing or bone marrow testing)

   • Chronic phase CML is defined as follows:

     • 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 × 109/L (≥ 50,000/mm3) (But, transient prior therapy related thrombocytopenia [<50 × 109/L (< 50,000/mm3)] is acceptable)

             • No extramedullary involvement other than enlargements of liver and spleen
3. Patients with positive Philadelphia chromosome and confirmed expression of BCR:ABL1 transcript
4. ECOG scale 0, 1 or 2

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
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.
8. Patients providing written informed consent form before the study related screening procedures.

Exclusion Criteria:

1. Patients with Philadelphia chromosome negative
2. Patients who used Radotinib for 8 days or longer before study entry
3. Patients who had been treated with other targeted anti-cancer therapy, except for Hydrea or Agrylin, which inhibits the growth of leukemic cells
4. Patients who have hypersensitivity to active ingredient or any of the excipients of this investigational product.

5. Patients with impaired cardiac function as defined below:

   • 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

           • The mean QTcF >450msec ECG tests at baseline

             • Clinically significant resting bradycardia (< 50 bpm) History of, or presence of symptomatic ventricular or atrial tachyarrhythmias

               • Clinically significant resting bradycardia (< 50 bpm)

                 • Medical history of clinically confirmed myocardial or infarctionof unstable angina (within last 12 months)

                   • Other clinically significant cardiac disease (e.g. congestive heart failure, or uncontrolled hypertension)
6. Cytologically confirmed CNS involvement (if asymptomatic, spinal fluid examination is not necessary prior to first treatment)
7. Severe or uncontrolled chronic medical condition (e.g., uncontrolled diabetes, active or uncontrolled infection)
8. Other significant congenital or acquired bleeding disorders that are not related to underlying leukemia
9. Patients who previously received radiotherapy to at least 25% of the bone marrow
10. Patients who had a major surgery within 4 weeks prior to study entry or has not recovered from side effects of such surgery
11. Patients who diagosed with another clinically significant malignant tumor wihin 5years before study etnry, excluding basal cell carcinoma
12. Patients who are currently receiving treatment with a strong CYP3A4 inhibitor (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil) or CYP3A4 inducer (e.g., dexamthasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John's Wort). Treatment cannot be safely discontinued or switched to a different medication prior to initiation of study treatment
13. Patients who are currently receiving treatment with a medication that has the potential to prolong the QT interval. Treatment cannot be safely discontinued or switched to a different medication prior to initiation of study treatment
14. Impairment of GI function or GI disease that may significantly alter absorption of study drugs (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, GI bypass surgery).
15. History of acute or chronic pancreatitis within last one year
16. Acute or chronic liver or pancreas disease or severe renal disease

17. Patients with HbsAg, HCV Ab positive

    • following subjects can be enrolled.

      • Inactive hepatitis B surface antigen (HBsAg) carriers(site specific local lab normal range lower limit assessed by investigator)
      • undergoding HCV Ab or HCV RNA testing judged by investigator to be eligible for enroll
18. History of HIV Ab positive or confirmed HIV Ab positvie.
19. Pregnant or the women with breast-feeding 2

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate MMR rate up to 12months following the treatment of Radotinib	up to 12months

Collaborators and Investigators

• Sponsor: Il-Yang Pharm. Co., Ltd.
• Investigators: Study Director: Na Yun Kim, Il-Yang Pharm. Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 28, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: RT51KR-IIT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No