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

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ClinicalTrials.gov Identifier: NCT02629692
Recruitment Status : Recruiting
First Posted : December 14, 2015
Last Update Posted : April 28, 2022
Sponsor:
Information provided by (Responsible Party):
Sun Pharma Advanced Research Company Limited

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

Condition or disease Intervention/treatment Phase
Healthy (For Part A) Chronic Myeloid Leukemia (for Part B and C) Drug: Vodobatinib (K0706) capsules Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 303 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

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 refractory CML
Masking: None (Open Label)
Masking Description:

Part B and C: Single arm (Open-label)

Part A: 2 arms: Investigational agent arm and Placebo arm (Double-blind).
Primary Purpose: Treatment
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)
Actual Study Start Date : April 25, 2017
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Vodobatinib (K0706) capsules Drug: Vodobatinib (K0706) capsules

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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    PART B

  2. Incidence and severity of treatment emergent AEs as assessed by CTCAE v4.03 [ Time Frame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) ]
    PART B

  3. For CML subjects in CP at study entry [ Time Frame: 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

  4. For CML subjects in AP at study entry [ Time Frame: 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

  5. For CML subjects in BP at study entry [ Time Frame: 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 :
  1. 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) ]
    PART B and PART C

  2. 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) ]
    PART B and PART C

  3. 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) ]
    PART B and PART C

  4. 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) ]
    PART C

  5. 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) ]
    PART C

  6. 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) ]
    PART C

  7. 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) ]
    PART C

  8. 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 ]
    Part C

  9. 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) ]
    PART C

  10. 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) ]
    PART C

  11. 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) ]
    PART C

  12. 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) ]
    PART C

  13. In all subjects Overall survival (OS) [ Time Frame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) ]
    PART C

  14. 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) ]
    PART C


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02629692


Contacts
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Contact: Head, Clinical development +9122 66455645 ext 5678 clinical.trials@sparcmail.com

Locations
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Sponsors and Collaborators
Sun Pharma Advanced Research Company Limited
More Information
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Responsible Party: Sun Pharma Advanced Research Company Limited
ClinicalTrials.gov Identifier: NCT02629692    
Other Study ID Numbers: CLR_15_03 V 12 Amendment 12
First Posted: December 14, 2015    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sun Pharma Advanced Research Company Limited:
CML
Chronic Myelogenous Leukemia
K0706
Vodobatinib
 ponatinib-refractory/intolerant
treatment refractory chronic myeloid leukemia
Ponatinib
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
 Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases