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

Phase 1

Active, not recruiting

• Conditions: Healthy (For Part A); Chronic Myeloid Leukemia (for Part B and C)
• Interventions: Drug: Vodobatinib (K0706) capsules

• 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.

Study Timeline

• Study First Submitted: 2015-12-10
• Study First Submitted QC: 2015-12-10
• Study First Posted: 2015-12-14
• Study Start: 2016-06-27
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-30
• Last Update Posted: 2024-07-31
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

• 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).

Exclusion Criteria

• 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)

The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute; 🇺🇸 Downey, California, United States

UCLA Hematologic Malignancy Program; 🇺🇸 Los Angeles, California, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Board of Regents of the University System of Georgia; 🇺🇸 Augusta, Georgia, United States

Memorial Sloan Kettering Cancer Center - MAIN; 🇺🇸 New York, New York, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Huntsman Cancer Institute University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Cliniques Universitaires Saint-Luc; 🇧🇪 Bruxelles, Belgium

Institut Paoli Calmettes; 🇫🇷 Marseille Cedex 9, Bouches-du-Rhône, France

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