Description:
Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic
activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML
Title
- Brief Title: Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment Refractory/Intolerant CML Failing ≥3 Prior CML Therapies
- Official Title: A Two-Part Phase 1/2 Study to Determine Safety, Tolerability, Pharmacokinetics, and Activity of K0706, a Novel Tyrosine Kinase Inhibitor (TKI), in Healthy Subjects and in Subjects With Chronic Myeloid Leukemia (CML) or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Clinical Trial IDs
- ORG STUDY ID:
CLR_15_03 V 12 Amendment 12
- NCT ID:
NCT02629692
Conditions
- Healthy (For Part A)
- Chronic Myeloid Leukemia (for Part B and C)
Interventions
| Drug | Synonyms | Arms |
|---|
| Vodobatinib (K0706) capsules | | Vodobatinib (K0706) capsules |
Purpose
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 ongoing in India
and Korea
Part C study in subjects with treatment-refractory/intolerant is enrolling globally.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Vodobatinib (K0706) capsules | Experimental | | - Vodobatinib (K0706) capsules
|
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | To determine the Maximum Tolerated Dose (MTD) as determined by frequency of Dose Limiting Toxicities |
| Time Frame: | Dose Limiting toxicities observed over a 4 week period |
| Safety Issue: | |
| Description: | PART B |
Secondary Outcome Measures
| Measure: | Pharmacokinetic profile of K0706 - Cmax [The maximum (peak) observed drug concentration after dose administration] |
| Time Frame: | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART B and PART C |
| Measure: | Pharmacokinetic profile of Vodobatinib (K0706) - Tmax [The time to reach maximum (peak) drug concentration after dose administration] |
| Time Frame: | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART B and PART C |
| Measure: | Pharmacokinetic profile of Vodobatinib (K0706) - Cmin [ Minimum observed drug concentration after dose administration] |
| Time Frame: | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART B and PART C |
| Measure: | In subjects with CML- CP:Proportion of subjects achieving Complete Hematological Response as assessed by complete blood count of peripheral blood sample |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | In subjects with CML- CP:Proportion of subjects achieving Complete Cytogenetic Response as assessed by conventional Karyotyping of Bone marrow aspirate |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | 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) |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | In subjects with CML-AP & BP: Proportion of subjects achieving Complete cytogenetic response as assessed by conventional Karyotyping of Bone marrow aspirate |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | In subjects with CML-AP & BP: Proportion of subjects achieving Partial Cytogenetic Response (PCyR) as assessed by conventional Karyotyping of Bone marrow aspirate |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of K0706 |
| Safety Issue: | |
| Description: | Part C |
| Measure: | 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) |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | 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 |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | 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 |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | In all subjects Progression free survival (PFS) |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | In all subjects Overall survival (OS) |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
| Measure: | Incidence and severity of treatment emergent AEs as assessed by CTCAE v5.0 |
| Time Frame: | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |
| Safety Issue: | |
| Description: | PART C |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Sun Pharma Advanced Research Company Limited |
Trial Keywords
- CML
- Chronic Myelogenous Leukemia
- K0706
- Vodobatinib
- ponatinib-refractory/intolerant
- treatment refractory chronic myeloid leukemia
- Ponatinib
Last Updated
February 25, 2021
