Clinical Trials /

Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment Refractory/Intolerant CML Failing ≥3 Prior CML Therapies

NCT02629692

Description:

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

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Vodobatinib (K0706) capsulesVodobatinib (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

NameTypeDescriptionInterventions
Vodobatinib (K0706) capsulesExperimental
  • 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