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This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Ph+ Chronic Myeloid Leukemia (CML) who have relapsed or are refractory or intolerant to a Tyrosine Kinase Inhibitor (TKI).
This study is a global, open label Phase 1b/2 to determine the efficacy and safety of KRT-232 in patients with chronic phase CML (CML-CP) and accelerated phase (CML-AP) who have failed TKI treatments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP | Experimental | KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule. |
|
| Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP) | Experimental | KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasastinib will be administered orally, per locally prescribed dose and schedule. |
|
| Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP) | Experimental | KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Nilotinib will be administered orally, per locally prescribed dose and schedule. |
|
| Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP) | Experimental | KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KRT-232 | Drug | KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232 | DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib | 28 Days |
| Part 2, Arm A and B: Major molecular response (MMR) rate | The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria | 6 months |
| Part 2, Arm C: Major hematological response (MaHR) rate | The proportion of subjects who achieved MaHR according to modified ELN criteria | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| CCyR rate | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B | 12 months |
| MCyR rate | The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C |
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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 |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Birmingham | Recruiting | Birmingham | Alabama | 35294 | United States | |
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| Dasatinib | Drug | Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth. |
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| Nilotinib | Drug | Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth. |
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| 47 months |
| Duration of response | DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first | 47 months |
| Rate of complete hematologic response (CHR) | The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B | 47 months |
| Progression-free survival (PFS) in each Arm | PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first | 47 months |
| Overall survival (OS) in each Arm | OS is defined as the time from the first treatment dose date to death from any cause | 47 months |
| Georgia Cancer Center at Augusta University |
| Recruiting |
| Augusta |
| Georgia |
| 30912 |
| United States |
| University of Pittsburgh Medical Center | Recruiting | Pittsburgh | Pennsylvania | 15232 | United States |
| Texas Oncology- Sammons CC at Baylor | Recruiting | Dallas | Texas | 75246 | United States |
| Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
| Princess Margaret Cancer Center | Recruiting | Toronto | Ontario | M5G 2C1 | Canada |
| Centre Leon Berard | Recruiting | Lyon | 69008 | France |
| APHM Hopital de la Timone | Recruiting | Marseille | 13005 | France |
| Institut Paoli-Calmettes | Recruiting | Marseille | 13009 | France |
| Centre Hospitalier Lyon Sud | Recruiting | Saint-Genis-Laval | 69310 | France |
| Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda | Recruiting | Milan | MI | 20122 | Italy |
| Azienda Ospedaliero - Universitaria Mater Domini | Recruiting | Catanzaro | 88100 | Italy |
| Istituto Romagnolo per lo Studio dei Tumori Dino Amadori | Recruiting | Meldola FC | 47014 | Italy |
| Fondazione IRCCS Policlinico San Matteo | Recruiting | Pavia | 27100 | Italy |
| Pratia Onkologia Katowice | Recruiting | Katowice | 40-519 | Poland |
| National Medical Research Center of Hematology | Recruiting | Moscow | 125167 | Russia |
| Almazov National Medical Research Center | Recruiting | Saint Petersburg | 197341 | Russia |
| Samara State Medical University | Recruiting | Samara | 443001 | Russia |
| Kyungpook National University Hospital | Recruiting | Daegu | South Korea |
| Samsung Medical Center | Recruiting | Seoul | 135-710 | South Korea |
| Seoul National University Hospital | Recruiting | Seoul | South Korea |
| Severance Hospital | Recruiting | Seoul | South Korea |
| ClĂnica Universidad de Navarra | Recruiting | Madrid | Navarre | 28027 | Spain |
| Clinica Universidad de Navarra | Recruiting | Pamplona | Navarre | 31008 | Spain |
| Hospital Universitari Vall d'Hebron | Recruiting | Barcelona | 08035 | Spain |
| Hospital Universitario La Paz | Recruiting | Madrid | 28046 | Spain |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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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 |
| D000069439 | Dasatinib |
| C498826 | nilotinib |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
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