Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥3 Prior CML Therapies

NCT02629692 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: CLR_15_03 V 12 Amendment 12
• Study Type: interventional
• Target: 122
• Locations: 11 countries
• Sites: 38

Brief Summary

Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML

Conditions

Healthy (For Part A); Chronic Myeloid Leukemia (for Part B and C)

Keywords

CML; Chronic Myelogenous Leukemia; K0706; Vodobatinib; ponatinib-refractory/intolerant; treatment refractory chronic myeloid leukemia; Ponatinib

Outcome Measures

Primary Outcomes (5)

• To determine the Maximum Tolerated Dose (MTD) as determined by frequency of Dose Limiting Toxicities

  PART B

  Dose Limiting toxicities observed over a 4 week period

• Incidence and severity of treatment emergent AEs as assessed by CTCAE v4.03

  PART B

  All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)

• For CML subjects in CP at study entry

  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

  All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)

• For CML subjects in AP at study entry

  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

  All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)

• For CML subjects in BP at study entry

  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

  All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)

Secondary Outcomes (14)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (1)

Vodobatinib (K0706) capsules

EXPERIMENTAL

Drug: Vodobatinib (K0706) capsules

Interventions

Vodobatinib (K0706) capsules DRUG

Part A: Vodobatinib (K0706) capsules in single ascending doses. Part B: Oral Vodobatinib (K0706) capsules in multiple ascending doses, once daily. Part C: Oral Vodobatinib (K0706) capsules at recommended phase 2 dose of 174 mg, once daily.

Vodobatinib (K0706) capsules

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sun Pharma Advanced Research Company Limited: lead

Study Sites (38)

The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute

Downey, California, 90241, United States

Location

UCLA Hematologic Malignancy Program

Los Angeles, California, 90024, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Board of Regents of the University System of Georgia

Augusta, Georgia, 30912, United States

Location

Memorial Sloan Kettering Cancer Center - MAIN

New York, New York, 10065, United States

Location

Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute University of Utah

Salt Lake City, Utah, 84112, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Institut Paoli Calmettes

Marseille, Bouches-du-Rhône, 13273, France

Location

Centre Léon Bérard

Lyon, Rhone, 69373, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhone, 69495, France

Location

Debreceni Egyetem

Debrecen, 4032, Hungary

Location

Prince Aly Khan Hospital

Mumbai, Maharashtra, 400010, India

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

Location

Sahyadri Specialty Hospital

Pune, Maharashtra, 411004, India

Location

Meenakshi Mission Hospital & Research Centre

Madurai, Tamil Nadu, 625107, India

Location

Tata Medical Centre

Kolkata, West Bengal, 700156, India

Location

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Forli - Cesena, 47014, Italy

Location

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)

Monza, Milano, 20900, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale Sant'Eugenio

Roma, 00144, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Roma, 00161, Italy

Location

Spitalul Clinic Colentina

Bucharest, 020125, Romania

Location

Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca

Cluj-Napoca, 400124, Romania

Location

Spitalul Clinic Municipal Filantropia Craiova

Craiova, 200143, Romania

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Gyeonggi-do, 06591, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Gyeonggi-do, 6591, South Korea

Location

Uijeongbu Eulji Medical Center, Eulji University

Gyeonggi-do, 11759, South Korea

Location

ICO Badalona - Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hacettepe University Hospital

Altındağ, 06230, Turkey (Türkiye)

Location

Kayseri Erciyes University Hospital

Kayseri, 38039, Turkey (Türkiye)

Location

King's College Hospital

London, Greater London, SE5 9NU, United Kingdom

Location

Hammersmith Hospital

London, Greater London, W120HS, United Kingdom

Location

Related Publications (1)

• Cortes JE, Kim DW, Saikia T, Khattry N, Rathnam K, Alvarado Y, Hannah G, Tantravahi SK, Apperley JF, Charbonnier A, Garcia-Gutierrez V, Lucchesi A, Dima D, Illes A, Popov VM, Abruzzese E, Nag A, Apte S, Badar T, Yao SL, Saxena U, Sreenivasan J, Inamdar S, Chimote G, Nicolini FE. Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2025 Mar;12(3):e201-e213. doi: 10.1016/S2352-3026(24)00354-5. Epub 2025 Feb 7.

  PMID: 39929221 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Capsules

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Part B and C: Single arm (Open-label) Part A: 2 arms: Investigational agent arm and Placebo arm (Double-blind).
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Single ascending dose in healthy volunteers. Part B: Multiple ascending dose safety and tolerability study in subjects with CML or Ph + ALL. Part C: Efficacy and safety study in subjects with treatment-resistant CML

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 14, 2015
• Study Start: June 27, 2016
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2); RO (3); IT (5); KR (3); FR (3); HU (1); ES (5); US (8); IN (5); BE (1); GB (2)