Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
Myelofibrosis, Primary Myelofibrosis, Post-PV MF
About this trial
This is an interventional treatment trial for Myelofibrosis focused on measuring Myelofibrosis
Eligibility Criteria
Inclusion Criteria:
Subjects with suboptimal response to ruxolitinib:
- Treatment with at a stable dose of ruxolitinib prior to study entry
- Subjects ≥ 18 years of age and able to provide informed consent.
- Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
- High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
- Palpable spleen measuring ≥ 5 cm below the left lower coastal margin (LLCM) or spleen volume of ≥ 450 cm3 by MRI or CT scan assessment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Adequate hematological, hepatic, & renal function.
Exclusion Criteria:
Treatment-naive subjects:
- Prior treatment with any JAKi
Subjects with suboptimal response to ruxolitinib:
- Documented disease progression while on ruxolitinib treatment
All subjects:
- Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
- Prior treatment with a BTK or BMX inhibitor
Sites / Locations
- University of Alabama at BirminghamRecruiting
- Gabrail Cancer CenterRecruiting
- University of Cincinnati (UC)Recruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- CHU AngersRecruiting
- AP-HM - Hôpital de la TimoneRecruiting
- CHU de Nice - Hopital L'Archet IIRecruiting
- Hôpital Saint Louis - AP-HPRecruiting
- Centre Hospitalier Lyon SudRecruiting
- Marien Hospital DuesseldorfRecruiting
- Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum HallRecruiting
- IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'OrsolaRecruiting
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di MilanoRecruiting
- Azienda Ospedaliera di Perugia-Ospedale S. Maria della MisericordiaRecruiting
- Pratia Onkologia KatowiceRecruiting
- Hospital Universitari Arnau de VilanovaRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Hospital Universitario Virgen de la VictoriaRecruiting
- Hospital Quironsalud de ZaragozaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Phase 1b - Dose Level 1
Phase 1b - Dose Level 2
Phase 1b - Dose Level 3
Phase 2 - Cohort 1 JAKi treatment-naïve MF
Phase 2 - Cohort 2 suboptimal response to Ruxolitinib
150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib.
The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose of ruxolitinib will be based on the subject's baseline platelet count.
The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle. The dose schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study.