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| Name | Class |
|---|---|
| Telios Pharma, Inc. | INDUSTRY |
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This study evaluates KRT-232 in Combination With TL-895 for the Treatment of Relapsed or Refractory Myelofibrosis and KRT-232 for the Treatment of JAK Inhibitor Intolerant Myelofibrosis.
Cohorts 1 and 2 will undergo dose finding and dose expansion. Eligible patients will be randomly assigned to an open cohort, either Cohort 1 or Cohort 2. Cohort 3 will be conducted as a dose expansion, independent of Cohorts 1 and 2.
Cohort 1 will follow a 3+3 dose escalation design to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D) of TL-895 administered QD in combination with KRT-232. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.
Cohort 2 will follow a 3+3 dose escalation design to determine the MTD/MAD and recommended RP2D of TL-895 administered BID in combination with KRT-232. An SRC will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.
Cohort 3 will be conducted a 2-stage design. In stage 1, enrollment will continue until 15 evaluable patients have been enrolled. An SRC will review the data during the study and if there are ≥4 responders based on the futility criteria and safety data from Stage 1, Cohort 3 expansion will commence. If there are ≤3 patients responding to therapy, Cohort 3 will be terminated. Once expansion criteria have been met, Cohort 3 will be expanded to a total of 46 evaluable patients for Stage 2 analyses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (R/R MF), Dose Level 1 | Experimental | 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. |
|
| Cohort 1 (R/R MF), Dose Level 2 | Experimental | 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. |
|
| Cohort 2 (R/R MF), Dose Level 1 | Experimental | 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. |
|
| Cohort 2 (R/R MF), Dose Level 2 | Experimental | 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. |
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| Cohort 3 (JAKi Intolerant MF) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KRT-232 | Drug | KRT-232, administered by mouth |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b - The MTD/MAD and RP2D of TL-895 in combination with KRT-232 in patients with R/R MF (Cohort 1 and Cohort 2) | DLTs will be used to establish the MTD. RP2D will be determined by the SRC based on safety data from the combination of TL-895 and KRT-232. | 56 Days |
| Phase 2 - Spleen response rate for each cohort | A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 24 | 24 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Total Symptom Score (TSS) | The change in TSS based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) | 24 Weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| John Mei | Contact | 650-542-0136 | jmei@kartosthera.com | |
| Irene Dea | Contact | (650) 839-7341 | idea@kartosthera.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham School of Medicine, Division of Hematology and Oncology | Recruiting | Birmingham | Alabama | 35233 | United States |
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| Experimental |
KRT-232 at 240mg will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. |
|
| TL-895 | Drug | TL-895, administered by mouth |
|
| The Oncology Institute of Hope | Recruiting | Whittier | California | 90603 | United States |
| Lake City Cancer Center | Recruiting | Lake City | Florida | 32024 | United States |
| Carle Cancer Center | Recruiting | Urbana | Illinois | 61801 | United States |
| Columbia University Medical Center | Recruiting | Fort Lee | New Jersey | 07024 | United States |
| Memorial Sloan Kettering Cancer Center (MSKCC) | Recruiting | New York | New York | 10065 | United States |
| LKH Hochsteiermark | Recruiting | Leoben | 8700 | Austria |
| Meduni Wien, Univ. Klinik für Innere Medizin I | Recruiting | Vienna | 1090 | Austria |
| University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski, Pleven | Recruiting | Pleven | 5800 | Bulgaria |
| University Multiprofile Hospital for Active Treatment Dr. Georgi Plovdiv | Recruiting | Plovdiv | 4002 | Bulgaria |
| Hematology Clinic Specialized Hospital for Active Treatment of Hematological Diseases, Sofia | Recruiting | Sofia | 1756 | Bulgaria |
| Chu Amiens Picardie Site Sud | Recruiting | Amiens | 80054 | France |
| CHU de Limoges Service Hématologie Clinique et Thérapie Cellulaire | Recruiting | Limoges | 87042 | France |
| CHU Nantes - Hôtel Dieu | Recruiting | Nantes | 44093 | France |
| CHU de Nice Hospital | Recruiting | Nice | 06200 | France |
| Hôpital Saint Louis | Recruiting | Paris | 75475 | France |
| Centre Hospitalier Lyon Sud | Recruiting | Pierre-Bénite | 63310 | France |
| University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology | Recruiting | Halle | 06120 | Germany |
| University Hospital Marburg, Department of Hematology, Oncology and Immunology | Recruiting | Marburg | 35043 | Germany |
| Moritz Kaposi General Hospital, Department of Hematology | Recruiting | Kaposvár | H-7400 | Hungary |
| Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Hematology | Recruiting | Nyíregyháza | H-4400 | Hungary |
| Medical Center of the University of Pecs, 1st Department of Internal Medicine, Division of Hematology | Recruiting | Pécs | H-7624 | Hungary |
| Fejer County St. Gyorgy University Teaching Hospital, Department of Internal Medicine III, Hematology | Recruiting | Székesfehérvár | H-8000 | Hungary |
| Polyclinic S. Orsola-Malpighi | Recruiting | Bologna | 40138 | Italy |
| ASST Spedali Civili di Brescia | Recruiting | Brescia | 25123 | Italy |
| Careggi University Hospital | Recruiting | Florence | 50134 | Italy |
| Hospital Casa Sollievo della Sofferenza, Department of Oncology and Hematology, Division of Hematology | Recruiting | Foggia | 71013 | Italy |
| Hospital of Ravenna, Operative Unit of Hematology | Recruiting | Ravenna | 48121 | Italy |
| Jan Biziel University Hospital #2 in Bydgoszcz, Department of Hematology | Recruiting | Bydgoszcz | 85-168 | Poland |
| Pratia Onkologia Katowice | Recruiting | Katowice | 40-519 | Poland |
| Frederic Chopin Provincial Teaching Hospital No. 1 in Rzeszow, Department of Hematology | Recruiting | Rzeszów | 35-055 | Poland |
| Slupsk Provincial Specialist Hospital n.a. Janusz Korczak, Department of Hematology | Recruiting | Słupsk | 76-200 | Poland |
| Nasz Lekarz Medical Outpatient Clinics Slawomir Jeka | Recruiting | Torun | 87-100 | Poland |
| Clinical Center of Serbia | Recruiting | Belgrade | 11000 | Serbia |
| Clinical Center of Vojvodina | Recruiting | Novi Sad | 21000 | Serbia |
| Hematologia Clínica | Recruiting | Barcelona | 08003 | Spain |
| University Clinical Hospital of Salamanca, Department of Hematology | Recruiting | Salamanca | 37007 | Spain |
| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000723723 | navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid |
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