KRT-232 in Combination With TL-895 for the Treatment of R/R MF and KRT-232 for the Treatment of JAKi Intolerant MF
Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Relapsed/Refractory Myelofibrosis, Janus associated Kinase Inhibitor-Intolerant Myelofibrosis, MDM2, navtemadlin
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, (WHO 2016)
- ECOG ≤ 2
- Cohort 1 and Cohort 2: R/R following JAK inhibitor treatment
- Cohort 3: patients who are intolerant to JAK inhibitor treatment
Exclusion Criteria:
- Prior treatment with MDM2 inhibitors or p53-directed therapies
- Prior treatment with a BCR-ABL, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR), bromodomain and extraterminal domain (BET), histone deacetylase (HDAC), or spleen tyrosine kinase (Syk) inhibitor
- Prior splenectomy
- Splenic irradiation within 3 months prior to the first dose of study treatment
- Clinically significant thrombosis within 3 months of screening
- Grade 2 or higher QTc prolongation
Sites / Locations
- University of Alabama at Birmingham School of Medicine, Division of Hematology and OncologyRecruiting
- The Oncology Institute of HopeRecruiting
- Lake City Cancer CenterRecruiting
- Carle Cancer CenterRecruiting
- Columbia University Medical CenterRecruiting
- Memorial Sloan Kettering Cancer Center (MSKCC)Recruiting
- LKH HochsteiermarkRecruiting
- Meduni Wien, Univ. Klinik für Innere Medizin IRecruiting
- University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, PlevenRecruiting
- University Multiprofile Hospital for Active Treatment Dr. Georgi PlovdivRecruiting
- Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, SofiaRecruiting
- Chu Amiens Picardie Site SudRecruiting
- CHU de Limoges Service Hématologie Clinique et Thérapie CellulaireRecruiting
- CHU Nantes - Hôtel DieuRecruiting
- CHU de Nice HospitalRecruiting
- Hôpital Saint LouisRecruiting
- Centre Hospitalier Lyon SudRecruiting
- University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and OncologyRecruiting
- University Hospital Marburg, Department of Hematology, Oncology and ImmunologyRecruiting
- Moritz Kaposi General Hospital, Department of HematologyRecruiting
- Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of HematologyRecruiting
- Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of HematologyRecruiting
- Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, HematologyRecruiting
- Polyclinic S. Orsola-MalpighiRecruiting
- ASST Spedali Civili di BresciaRecruiting
- Careggi University HospitalRecruiting
- Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of HematologyRecruiting
- Hospital of Ravenna, Operative Unit of HematologyRecruiting
- Jan Biziel University Hospital #2 in Bydgoszcz, Department of HematologyRecruiting
- Pratia Onkologia KatowiceRecruiting
- Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of HematologyRecruiting
- Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of HematologyRecruiting
- Nasz Lekarz Medical Outpatient Clinics Slawomir JekaRecruiting
- Clinical Center of SerbiaRecruiting
- Clinical Center of VojvodinaRecruiting
- Hematologia ClínicaRecruiting
- University Clinical Hospital of Salamanca, Department of HematologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1 (R/R MF), Dose Level 1
Cohort 1 (R/R MF), Dose Level 2
Cohort 2 (R/R MF), Dose Level 1
Cohort 2 (R/R MF), Dose Level 2
Cohort 3 (JAKi Intolerant MF)
TL-895 at 200 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
TL-895 at 300 mg once a day (QD) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
TL-895 at 100 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
TL-895 at 150 mg twice a day (BID) continuously starting on Cycle 1 Day 1 in a 28-day cycle. KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle starting on Cycle 2 Day 1.
KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.