Chronic Myeloid Leukemia (for Part B and C) Clinical Trial
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)
| Verified date | October 2023 |
| Source | Sun Pharma Advanced Research Company Limited |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML
| Status | Active, not recruiting |
| Enrollment | 122 |
| Est. completion date | August 2026 |
| Est. primary completion date | August 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Cliniques Universitaires Saint-Luc | Bruxelles | |
| France | CHU Angers - Hôpital Hôtel Dieu | Angers | Maine Et Loire |
| France | Hopital Claude Huriez - CHRU Lille | Lille cedex | Nord |
| France | Centre Léon Bérard | Lyon Cedex 08 | Rhone |
| France | Institut Paoli Calmettes | Marseille Cedex 9 | Bouches-du-Rhône |
| France | CHU de Nantes - Hotel Dieu | Nantes cedex 1 | Loire Atlantique |
| France | Hôpital Saint-Louis | Paris cedex 10 | Paris |
| France | Centre Hospitalier Lyon Sud | Pierre-Bénite | Rhone |
| France | CHU Poitiers - Hôpital la Milétrie | Poitiers | Vienne |
| France | CHU Rennes - Hopital Pontchaillou | Rennes cedex 9 | Ille Et Vilaine |
| France | CHU Amiens - Hopital Sud | Salouel | Somme |
| France | CHU de Nancy - Hôpital de Brabois Adultes | Vandœuvre-lès-Nancy | Meurthe Et Moselle |
| Hungary | Semmelweis Egyetem | Budapest | |
| Hungary | Debreceni Egyetem | Debrecen | |
| Hungary | SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz | Nyiregyhaza | |
| Hungary | Pecsi Tudomanyegyetem | Pecs | |
| India | Tata Medical Centre | Kolkata | West Bengal |
| India | Meenakshi Mission Hospital & Research Centre | Madurai | Tamilnadu |
| India | Prince Aly Khan Hospital | Mumbai | Maharashtra |
| India | Tata Memorial Hospital | Mumbai | Maharashtra |
| India | Sahyadri Specialty Hospital | Pune | Maharashtra |
| Italy | Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Ferrarotto Alessi) | Catania | |
| Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
| Italy | Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori | Meldola | Forli - Cesena |
| Italy | Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico | Milano | |
| Italy | Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza | Roma | |
| Italy | Ospedale Sant'Eugenio | Roma | |
| Korea, Republic of | Uijeongbu Eulji Medical Center, Eulji University | Gyeonggi-do | |
| Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Gyeonggi-do |
| Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Gyeonggi-do |
| Romania | Spitalul Clinic Colentina | Bucuresti | |
| Romania | Spitalul Clinic Coltea | Bucuresti | |
| Romania | Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca | Cluj-Napoca | |
| Romania | Spitalul Clinic Municipal Filantropia Craiova | Craiova | |
| Romania | Spitalul Clinic Judetean de Urgenta Targu Mures | Târgu Mure? | |
| Singapore | Singapore General Hospital | Singapore | |
| Spain | ICO Badalona - Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona |
| Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal | Madrid | |
| Spain | Hospital Clinico Universitario Virgen de la Victoria | Málaga | |
| Spain | Hospital Universitario Virgen del Rocio | Sevilla | |
| Turkey | Hacettepe University Hospital | Altindag | |
| Turkey | Kayseri Erciyes University Hospital | Kayseri | |
| United Kingdom | Hammersmith Hospital | London | Greater London |
| United Kingdom | King's College Hospital | London | Greater London |
| United States | Board of Regents of the University System of Georgia | Augusta | Georgia |
| United States | Baylor University Medical Center | Dallas | Texas |
| United States | The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute | Downey | California |
| United States | East Carolina University | Greenville | North Carolina |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | Indiana Blood Marro Transplant | Indianapolis | Indiana |
| United States | Mayo Clinic | Jacksonville | Florida |
| United States | UCLA Hematologic Malignancy Program | Los Angeles | California |
| United States | University of Southern California | Los Angeles | California |
| United States | Memorial Sloan Kettering Cancer Center - MAIN | New York | New York |
| United States | Huntsman Cancer Institute University of Utah | Salt Lake City | Utah |
| United States | New York Medical College | Valhalla | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Sun Pharma Advanced Research Company Limited |
United States, Belgium, France, Hungary, India, Italy, Korea, Republic of, Romania, Singapore, Spain, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | To determine the Maximum Tolerated Dose (MTD) as determined by frequency of Dose Limiting Toxicities | PART B | Dose Limiting toxicities observed over a 4 week period | |
| Primary | Incidence and severity of treatment emergent AEs as assessed by CTCAE v4.03 | PART B | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Primary | For CML subjects in CP at study entry | 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 | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Primary | For CML subjects in AP at study entry | 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 | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Primary | For CML subjects in BP at study entry | 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 | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | Pharmacokinetic profile of K0706 - Cmax [The maximum (peak) observed drug concentration after dose administration] | PART B and PART C | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) | |
| Secondary | Pharmacokinetic profile of Vodobatinib (K0706) - Tmax [The time to reach maximum (peak) drug concentration after dose administration] | PART B and PART C | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) | |
| Secondary | Pharmacokinetic profile of Vodobatinib (K0706) - Cmin [ Minimum observed drug concentration after dose administration] | PART B and PART C | All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706) | |
| Secondary | In subjects with CML- CP:Proportion of subjects achieving Complete Hematological Response as assessed by complete blood count of peripheral blood sample | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | In subjects with CML- CP:Proportion of subjects achieving Complete Cytogenetic Response as assessed by conventional Karyotyping of Bone marrow aspirate | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | 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) | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | In subjects with CML-AP & BP: Proportion of subjects achieving Complete cytogenetic response as assessed by conventional Karyotyping of Bone marrow aspirate | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | In subjects with CML-AP & BP: Proportion of subjects achieving Partial Cytogenetic Response (PCyR) as assessed by conventional Karyotyping of Bone marrow aspirate | Part C | All subjects will be followed up for 60 months from the first dose of K0706 | |
| Secondary | 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) | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | 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 | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | 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 | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | In all subjects Progression free survival (PFS) | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | In all subjects Overall survival (OS) | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) | |
| Secondary | Incidence and severity of treatment emergent AEs as assessed by CTCAE v5.0 | PART C | All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706) |