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

• Sponsor: Sun Pharma Advanced Research Company Limited (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT02629692
• Collaborator: (none)
• Enrollment: 303
• Locations: 70
• Arm: 1
• Anticipated Duration (Months): 111.2
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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

• Study Type: Interventional
• Anticipated 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 CMLPart 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: Apr 25, 2017
• Anticipated Primary Completion Date: Aug 1, 2022
• Anticipated Study Completion Date: Aug 1, 2026

Arms and Interventions

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

Primary Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

1. 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

2. 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

3. 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

4. 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

5. 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

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) [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 [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 [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) [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 [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 [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) [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) [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 [All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)]

    PART C

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute	Downey	California	United States	90241
2	UCLA Hematologic Malignancy Program	Los Angeles	California	United States	90024
3	University of Southern California	Los Angeles	California	United States	90033
4	Mayo Clinic	Jacksonville	Florida	United States	32224
5	Board of Regents of the University System of Georgia	Augusta	Georgia	United States	30912
6	IU Simon Cancer Center	Indianapolis	Indiana	United States	46202
7	Indiana Blood Marro Transplant	Indianapolis	Indiana	United States	46237
8	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	Memorial Sloan Kettering Cancer Center - MAIN	New York	New York	United States	10065
10	New York Medical College	Valhalla	New York	United States	10595
11	East Carolina University	Greenville	North Carolina	United States	27858
12	Baylor University Medical Center	Dallas	Texas	United States	75226
13	MD Anderson Cancer Center	Houston	Texas	United States	77030
14	Huntsman Cancer Institute University of Utah	Salt Lake City	Utah	United States	84112
15	ZNA Stuivenberg	Antwerpen		Belgium	2060
16	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
17	UZ Leuven	Leuven		Belgium	3000
18	Institut Paoli Calmettes	Marseille Cedex 9	Bouches-du-Rhône	France	13273
19	Institut Bergonié	Bordeaux cedex	Gironde	France	33076
20	CHU de Limoges - Hôpital Dupuytren	Limoges cedex	Haute Vienne	France	87042
21	CHU Rennes - Hopital Pontchaillou	Rennes cedex 9	Ille Et Vilaine	France	35033
22	CHU de Nantes - Hotel Dieu	Nantes cedex 1	Loire Atlantique	France	44000
23	CHU Angers - Hôpital Hôtel Dieu	Angers	Maine Et Loire	France	49033
24	CHU de Nancy - Hôpital de Brabois Adultes	Vandœuvre-lès-Nancy	Meurthe Et Moselle	France	54511
25	Hopital Claude Huriez - CHRU Lille	Lille cedex	Nord	France	59037
26	Hôpital Saint-Louis	Paris cedex 10	Paris	France	75475
27	Centre Léon Bérard	Lyon Cedex 08	Rhone	France	69373
28	Centre Hospitalier Lyon Sud	Pierre-Bénite	Rhone	France	69495
29	Hôpital Avicenne	Bobigny cedex	Seine Saint Denis	France	93009
30	CHU Amiens - Hopital Sud	Salouel	Somme	France	80480
31	CHU Poitiers - Hôpital la Milétrie	Poitiers	Vienne	France	86021
32	Semmelweis Egyetem	Budapest		Hungary	1083
33	Debreceni Egyetem	Debrecen		Hungary	4032
34	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza		Hungary	4400
35	Pecsi Tudomanyegyetem	Pecs		Hungary	7624
36	Prince Aly Khan Hospital	Mumbai	Maharashtra	India	400010
37	Tata Memorial Hospital	Mumbai	Maharashtra	India	400012
38	Sahyadri Specialty Hospital	Pune	Maharashtra	India	411004
39	Meenakshi Mission Hospital & Research Centre	Madurai	Tamilnadu	India	625107
40	Chittaranjan National Cancer Institute	Kolkata	West Bengal	India	700026
41	Tata Medical Centre	Kolkata	West Bengal	India	700156
42	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola	Forli - Cesena	Italy	47014
43	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza	Milano	Italy	20900
44	Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Ferrarotto Alessi)	Catania		Italy	95124
45	Azienda Ospedaliera Universitaria Careggi	Firenze		Italy	50134
46	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
47	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano		Italy	20162
48	Ospedale Sant'Eugenio	Roma		Italy	00144
49	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza	Roma		Italy	00161
50	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul	Gyeonggi-do	Korea, Republic of	06591
51	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul	Gyeonggi-do	Korea, Republic of	6591
52	Uijeongbu Eulji Medical Center, Eulji University	Gyeonggi-do		Korea, Republic of	11759
53	Spitalul Clinic Colentina	Bucuresti		Romania	020125
54	Spitalul Clinic Coltea	Bucuresti		Romania	030171
55	Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca	Cluj-Napoca		Romania	400124
56	Spitalul Clinic Municipal Filantropia Craiova	Craiova		Romania	200143
57	Spitalul Clinic Judetean de Urgenta Targu Mures	Târgu Mureș		Romania	540136
58	Singapore General Hospital	Singapore		Singapore	169856
59	ICO Badalona - Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
60	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
61	ICO Girona - Hospital Universitari de Girona Dr Josep Trueta	Girona		Spain	17007
62	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
63	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
64	Hospital Universitario La Paz	Madrid		Spain	28046
65	Hospital Clinico Universitario Virgen de la Victoria	Málaga		Spain	29010
66	Hospital Universitario de Salamanca	Salamanca		Spain	37007
67	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
68	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
69	King's College Hospital	London	Greater London	United Kingdom	SE5 9NU
70	Hammersmith Hospital	London	Greater London	United Kingdom	W120HS

Sponsors and Collaborators

• Sun Pharma Advanced Research Company Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Dec 14, 2015
• Last Update Posted: Apr 28, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

No Results Posted as of Apr 28, 2022