Philadelphia Chromosome Positive CML Patients Without Optimal Response or Tolerance to Bcr-Abl TKI

NCT01602952 | Completed Phase 1

• 1 other identifier: IY5511A1201
• Study Type: interventional
• Target: 85
• Locations: 3 countries
• Sites: 12

Brief Summary

A Phase I/II multicenter study of IY5511HCl in Philadelphia chromosome positive chronic myeloid leukemia patients without optimal response or tolerance to Bcr-Abl tyrosine kinase inhibitors (Imatinib and/ or Dasatinib, Nilotinib) In this study, The efficacy and safety of CML patients who are resistant or intolerable to imatinib in the Chronic and Accelerated phases. Phase 1 1\. To investigate the Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicity (DLT) of oral Radotinib HCl bid (twice daily) in the Philadelphia chromosome-positive CML subjects who are resistant, suboptimal responsive, or intolerant to imatinib OR resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously. Phase 2

1. 1.To investigate safety of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.
2. 2.To evaluate hematologic and cytogenetic efficacy of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Hematologic Diseases

Keywords

Radotinib; CML-CP, AP

Outcome Measures

Primary Outcomes (2)

• To investigate the Maximum Tolerated Dose(Phase 1)

  Radotinib will be given orally twice daily. Dose will be increased until it reaches MTD or the blood concentration of Radotinib stops rising

  12 month

• Rate of Complete hematologic response(CHR)(Phase 2)

  Main parameters for response assessment in the chronic and accelerated phases include Major Hematologic Responses (MR; No Evidence of Leukemia or NEL + Complete Hematologic Response or CHR) lasting for 4 weeks and at least one major cytogenetic response (MCyR)

  12 months

Secondary Outcomes (4)

• To investigate the Dose Limiting Toxicity(Phase 1)

  12 months

• Rate of complete Cytogenetic Response(CCyR)(Phase 2)

  12 months

• Adverse events(Phase 1& Phase 2)

  12 months

• Progression-free survival or PFS

  12 months

Study Arms (1)

Radotinib

EXPERIMENTAL

Phase 1 : 200mg/kg or 1200mg/m\^2 Phase 2 : 400mg Bid

Drug: Radotinib

Interventions

Radotinib DRUG

50mg, 100mg or 200mg Capsule BID

Also known as: IY5511HCl

Radotinib

Eligibility Criteria

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

You may qualify if:

• Phase I
• Age ≥ 18 years old
• Ph+ CML patients who are resistant at chronic, accelerate, and acute phase, or suboptimal responsive, or intolerant to imatinib or resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously.
• WHO Performance status of ≤2
• Patients must have the following laboratory values With normal liver and renal function
• Patients who have received interferon, other anti cancer drug or radiotherapy \> 1 week prior to starting study drug.
• Phase II
• Age ≥ 18 years old
• Ph+ CML patients in chronic or accelerated phase who are resistant or intolerant to Imatinib mesylate
• WHO Performance status of ≤2
• Patients must have the following laboratory values With normal liver and renal function
• Patients who have received interferon, other anti cancer drug or radiotherapy \> 1 week prior to starting study drug.

You may not qualify if:

• Phase I
• CNS infiltration
• Impaired cardiac function, including any one of the followings.
• LVEF \<45% as determined by MUGA scan or echocardiogram
• Clinically significant resting bradycardia
• Severe GI disease that may cause drug absorption problem of study drug
• Use of therapeutic Warfarin
• Acute or chronic liver or renal disease
• Other concurrent severe and/or uncontrolled medical conditions
• Treatment with any hematopoietic colony-stimulating growth factors ≤1 week prior to starting study drug.
• Patients who are currently receiving treatment with medications have the potential to prolong the QT interval
• Patients who have received Imatinib, interferon, other anti cancer drug or chemotherapy ≤ 1 week
• Patients who have received Nilotinib and Dasatinib ≤4 weeks prior to starting study drug.
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control.

Sponsors & Collaborators

• Il-Yang Pharm. Co., Ltd.: lead

Study Sites (12)

Local institution

Mumbai, Maharashtra, 741-234, India

Location

Local institution

Mumbai, Mazagaon, 512-364, India

Location

Local institution

Daegu, Buk-gu, 511-230, South Korea

Location

Local institution

Jeonju, Deokjin-gu, 212-789, South Korea

Location

Local institution

Ulsan, Dong-gu, 411-978, South Korea

Location

Local institution

Anyang-si, Dongan-gu, 751-231, South Korea

Location

Local institution

Hwasun, Hwasun-eup, 322-511, South Korea

Location

Local institution

Seoul, Jongro-ku, 231-855, South Korea

Location

Local institution

Busan, Seo-gu, 400-321, South Korea

Location

Seoul St. Mary's hospital

Seoul, Seocho-gu, South Korea

Location

Local institution

Suwon, Yeongtong-gu, 781-512, South Korea

Location

Local institution

Bangkok, Phyathai, 215-714, Thailand

Location

Related Publications (1)

• Kim SH, Menon H, Jootar S, Saikia T, Kwak JY, Sohn SK, Park JS, Jeong SH, Kim HJ, Kim YK, Oh SJ, Kim H, Zang DY, Chung JS, Shin HJ, Do YR, Kim JA, Kim DY, Choi CW, Park S, Park HL, Lee GY, Cho DJ, Shin JS, Kim DW. Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Haematologica. 2014 Jul;99(7):1191-6. doi: 10.3324/haematol.2013.096776. Epub 2014 Apr 4.

  PMID: 24705186 DERIVED

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Hematologic Diseases

Interventions

4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Translocation, Genetic; Chromosome Aberrations

Study Officials

• IL-yang Pharm

  IL-YANG Pharmaceutical.Co.,Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2012
• First Posted: May 21, 2012
• Study Start: July 1, 2008
• Primary Completion: October 1, 2012
• Study Completion: July 13, 2018
• Last Updated: August 29, 2018

Record last verified: 2018-08

Locations

KR (9); TH (1); IN (2)