Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥3 Prior CML Therapies
- Conditions
- Healthy (For Part A)Chronic Myeloid Leukemia (for Part B and C)
- Interventions
- Registration Number
- NCT02629692
- Lead Sponsor
- Sun Pharma Advanced Research Company Limited
- Brief Summary
Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML
- Detailed Description
Part A ( for Healthy volunteers) of the study is completed.
Part B dose-escalation study is completed. Recruitment in dose expansion is completed.
Part C study in subjects with treatment-resistant/intolerant is ongoing for the enrolled subjects.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 122
- Willing and able to give written, and dated, informed consent
- Male or female aged ≥ 18 years
- Willing and able to comply with the scheduled visits
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Subjects diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, who are resistant and/or intolerant to ≥ 3 prior TKIs one of which includes ponatinib (Part C).
- Presence of T315I (PART C)
- Any major surgery, as determined by the Investigator, within 4 weeks of IMP administration
- Inability to undergo venipuncture and/or tolerate venous access
- Positive exclusion tests: urine pregnancy tests (if applicable), HIV, hepatitis B surface antigen, or hepatitis C virus
- Known or suspected history of significant drug abuse as judged by the Investigator
- Received any other investigational agent within 30 days or a washout of at least 5 half-lives, whichever is longer of IMP administration
- Subjects who are eligible for potentially curative therapy that is available, including hematopoietic stem cell transplant
- Another primary malignancy within the past 3 years or earlier (except for adequately treated non-melanoma skin cancer or cervical cancer in situ
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Vodobatinib (K0706) capsules Vodobatinib (K0706) capsules -
- Primary Outcome Measures
Name Time Method Incidence and severity of treatment emergent AEs as assessed by CTCAE v4.03 All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART B
To determine the Maximum Tolerated Dose (MTD) as determined by frequency of Dose Limiting Toxicities Dose Limiting toxicities observed over a 4 week period PART B
For CML subjects in CP at study entry All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C: Proportion of subjects achieving Major Cytogenetic Response \[ defined as complete cytogenetic response (CCyR; 0% Ph+metaphases) or partial cytogenetic response (PCyR; 1-35% Ph+ metaphases)\] as assessed by conventional Karyotyping of Bone marrow aspirate
For CML subjects in AP at study entry All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C: Proportion of subjects achieving Major Hematologic Response \[ defined as complete hematologic response (CHR) or no evidence of leukemia (NEL)\] as assessed by complete blood count of peripheral blood sample
For CML subjects in BP at study entry All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C: Proportion of subjects achieving Major Hematologic Response \[defined as complete hematologic response (CHR) or no evidence of leukemia (NEL)\] as assessed by complete blood count of peripheral blood sample
- Secondary Outcome Measures
Name Time Method Pharmacokinetic profile of K0706 - Cmax [The maximum (peak) observed drug concentration after dose administration] All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) PART B and PART C
Pharmacokinetic profile of Vodobatinib (K0706) - Cmin [ Minimum observed drug concentration after dose administration] All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) PART B and PART C
In subjects with CML- CP:Proportion of subjects achieving Complete Hematological Response as assessed by complete blood count of peripheral blood sample All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
In subjects with CML-AP & BP: Proportion of subjects achieving Complete cytogenetic response as assessed by conventional Karyotyping of Bone marrow aspirate All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
Pharmacokinetic profile of Vodobatinib (K0706) - Tmax [The time to reach maximum (peak) drug concentration after dose administration] All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) PART B and PART C
In subjects with CML- CP:Proportion of subjects achieving Major Molecular Response as assessed by BCR-ABL transcript levels (BCR-ABL1 ratio of ≤ 0.1%) in peripheral blood using PCR (Polymerase Chain Reaction) All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
In subjects with CML-AP & BP: Proportion of subjects achieving Partial Cytogenetic Response (PCyR) as assessed by conventional Karyotyping of Bone marrow aspirate All subjects will be followed up for 60 months from the first dose of K0706 Part C
In subjects with CML- CP:Proportion of subjects achieving Complete Cytogenetic Response as assessed by conventional Karyotyping of Bone marrow aspirate All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
In subjects with CML-AP & BP: Proportion of subjects achieving Major Molecular Response as assessed by BCR-ABL transcript levels (BCR-ABL1 ratio of ≤ 0.1%) in peripheral blood using PCR (Polymerase Chain Reaction) All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
Time to Major Molecular Response : Time to MMR is the time from first dose to first MMR (BCR-ABL1 ratio of ≤ 0.1%) computed only for subjects who achieved MMR All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
In all subjects Progression free survival (PFS) All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
In all subjects Overall survival (OS) All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
Time to Major Cytogenetic Response (MCyR): Time to MCyR is the time from first dose to first MCyR (0-35% Ph+ metaphases) ; computed only for subjects who achieved MCyR All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
Incidence and severity of treatment emergent AEs as assessed by CTCAE v5.0 All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) PART C
Trial Locations
- Locations (37)
Prince Aly Khan Hospital
🇮🇳Mumbai, Maharashtra, India
Tata Memorial Hospital
🇮🇳Mumbai, Maharashtra, India
Sahyadri Specialty Hospital
🇮🇳Pune, Maharashtra, India
UCLA Hematologic Malignancy Program
🇺🇸Los Angeles, California, United States
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Spitalul Clinic Municipal Filantropia Craiova
🇷🇴Craiova, Romania
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Huntsman Cancer Institute University of Utah
🇺🇸Salt Lake City, Utah, United States
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
🇮🇹Monza, Milano, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Centre Léon Bérard
🇫🇷Lyon Cedex 08, Rhone, France
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
🇮🇹Roma, Italy
Uijeongbu Eulji Medical Center, Eulji University
🇰🇷Gyeonggi-do, Korea, Republic of
King's College Hospital
🇬🇧London, Greater London, United Kingdom
Kayseri Erciyes University Hospital
🇹🇷Kayseri, Turkey
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Ospedale Sant'Eugenio
🇮🇹Roma, Italy
Hammersmith Hospital
🇬🇧London, Greater London, United Kingdom
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Board of Regents of the University System of Georgia
🇺🇸Augusta, Georgia, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute
🇺🇸Downey, California, United States
Memorial Sloan Kettering Cancer Center - MAIN
🇺🇸New York, New York, United States
Institut Paoli Calmettes
🇫🇷Marseille Cedex 9, Bouches-du-Rhône, France
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, Rhone, France
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
🇮🇹Meldola, Forli - Cesena, Italy
ICO Badalona - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Meenakshi Mission Hospital & Research Centre
🇮🇳Madurai, Tamilnadu, India
Spitalul Clinic Colentina
🇷🇴Bucuresti, Romania
Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
Hacettepe University Hospital
🇹🇷Altındağ, Turkey
Tata Medical Centre
🇮🇳Kolkata, West Bengal, India