Clinical trial NCT02629692: Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Sun Pharma Advanced Research Company Limited
Sponsor class: INDUSTRY
First posted: 2015-12-14
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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-resistant CML
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To determine the Maximum Tolerated Dose (MTD) as determined by frequency of Dose Limiting Toxicities
timeFrame: Dose Limiting toxicities observed over a 4 week period
measure: Incidence and severity of treatment emergent AEs as assessed by CTCAE v4.03
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: For CML subjects in CP at study entry
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: For CML subjects in AP at study entry
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: For CML subjects in BP at study entry
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
Secondary outcomes:
measure: Pharmacokinetic profile of K0706 - Cmax [The maximum (peak) observed drug concentration after dose administration]
timeFrame: All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
measure: Pharmacokinetic profile of Vodobatinib (K0706) - Tmax [The time to reach maximum (peak) drug concentration after dose administration]
timeFrame: All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
measure: Pharmacokinetic profile of Vodobatinib (K0706) - Cmin [ Minimum observed drug concentration after dose administration]
timeFrame: All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
measure: In subjects with CML- CP:Proportion of subjects achieving Complete Hematological Response as assessed by complete blood count of peripheral blood sample
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: In subjects with CML- CP:Proportion of subjects achieving Complete Cytogenetic Response as assessed by conventional Karyotyping of Bone marrow aspirate
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
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)
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: In subjects with CML-AP & BP: Proportion of subjects achieving Complete cytogenetic response as assessed by conventional Karyotyping of Bone marrow aspirate
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: In subjects with CML-AP & BP: Proportion of subjects achieving Partial Cytogenetic Response (PCyR) as assessed by conventional Karyotyping of Bone marrow aspirate
timeFrame: All subjects will be followed up for 60 months from the first dose of K0706
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)
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
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
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
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
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: In all subjects Progression free survival (PFS)
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: In all subjects Overall survival (OS)
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
measure: Incidence and severity of treatment emergent AEs as assessed by CTCAE v5.0
timeFrame: All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
Other outcomes:
Locations:
city: Downey
country: United States
facility: The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute
state: California
city: Los Angeles
country: United States
facility: UCLA Hematologic Malignancy Program
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Augusta
country: United States
facility: Board of Regents of the University System of Georgia
state: Georgia
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - MAIN
state: New York
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute University of Utah
state: Utah
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
state: Bouches-du-Rhône
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
state: Rhone
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Mumbai
country: India
facility: Prince Aly Khan Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Specialty Hospital
state: Maharashtra
city: Madurai
country: India
facility: Meenakshi Mission Hospital & Research Centre
state: Tamilnadu
city: Kolkata
country: India
facility: Tata Medical Centre
state: West Bengal
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
state: Forli - Cesena
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
state: Milano
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Ospedale Sant'Eugenio
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
state: Gyeonggi-do
city: Gyeonggi-do
country: Korea, Republic of
facility: Uijeongbu Eulji Medical Center, Eulji University
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
city: Craiova
country: Romania
facility: Spitalul Clinic Municipal Filantropia Craiova
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Altındağ
country: Turkey
facility: Hacettepe University Hospital
city: Kayseri
country: Turkey
facility: Kayseri Erciyes University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
state: Greater London
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: Greater London
Study officials:
References: