Ignite Creation Date:
2025-12-25 @ 1:40 AM
Ignite Modification Date:
2025-12-27 @ 11:50 PM
Study NCT ID:
NCT04502394
Status:
UNKNOWN
Last Update Posted:
2022-08-04
First Post:
2020-07-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016403', 'term': 'Lymphoma, Large B-Cell, Diffuse'}, {'id': 'D015451', 'term': 'Leukemia, Lymphocytic, Chronic, B-Cell'}, {'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}], 'ancestors': [{'id': 'D016393', 'term': 'Lymphoma, B-Cell'}, {'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D015448', 'term': 'Leukemia, B-Cell'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000723723', 'term': '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'}, {'id': 'C000604908', 'term': 'acalabrutinib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 84}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2021-02-23', 'type': 'ACTUAL'}, 'statusVerifiedDate': '2022-08', 'completionDateStruct': {'date': '2024-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-08-03', 'studyFirstSubmitDate': '2020-07-27', 'studyFirstSubmitQcDate': '2020-08-05', 'lastUpdatePostDateStruct': {'date': '2022-08-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-08-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL', 'timeFrame': '56 Days', 'description': 'Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.'}, {'measure': 'Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)', 'timeFrame': '1 Year', 'description': 'Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.'}, {'measure': 'Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL', 'timeFrame': '1 Year', 'description': 'Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.'}], 'secondaryOutcomes': [{'measure': 'Phase 1b Secondary Objective: Pharmacokinetic (PK) profile', 'timeFrame': 'Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2', 'description': 'Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax).'}, {'measure': 'Phase 1b Secondary Objective: Pharmacokinetic (PK) profile', 'timeFrame': 'Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2', 'description': 'Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be area under the curve (AUC).'}, {'measure': 'Phase 1b Secondary Objective: Pharmacokinetic (PK) profile', 'timeFrame': 'Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2', 'description': 'Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be half-life (T1/2).'}, {'measure': 'Phase 1b Secondary Objective: Pharmacokinetic (PK) profile', 'timeFrame': 'Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2', 'description': 'Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be apparent clearance.'}, {'measure': 'Phase 1b Secondary Objective: Pharmacokinetic (PK) profile', 'timeFrame': 'Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2', 'description': 'Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.'}, {'measure': 'Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.', 'timeFrame': '2 Years', 'description': 'Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.'}, {'measure': 'Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects', 'timeFrame': '2 Years', 'description': 'Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['navtemadlin'], 'conditions': ['Diffuse Large B Cell Lymphoma', 'Chronic Lymphocytic Leukemia', 'Non Hodgkin Lymphoma']}, 'descriptionModule': {'briefSummary': 'This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior lines of treatment or 1 prior for patients who are ineligible for stem cell transplant\n* Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment\n* ECOG 0 to 2\n* Adequate hematologic, hepatic, and renal functions.\n\nExclusion Criteria:\n\n* Prior treatment with any MDM2 inhibitor\n* Prior treatment with any BTK inhibitor'}, 'identificationModule': {'nctId': 'NCT04502394', 'briefTitle': 'Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL', 'organization': {'class': 'INDUSTRY', 'fullName': 'Kartos Therapeutics, Inc.'}, 'officialTitle': 'An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia', 'orgStudyIdInfo': {'id': 'KRT-232-111'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1 (R/R DLBCL)', 'description': 'KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.\n\nAcalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.', 'interventionNames': ['Drug: KRT-232', 'Drug: acalabrutinib']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2 (R/R CLL)', 'description': 'KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.\n\nAcalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.', 'interventionNames': ['Drug: KRT-232', 'Drug: acalabrutinib']}], 'interventions': [{'name': 'KRT-232', 'type': 'DRUG', 'description': 'KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth', 'armGroupLabels': ['Cohort 1 (R/R DLBCL)', 'Cohort 2 (R/R CLL)']}, {'name': 'acalabrutinib', 'type': 'DRUG', 'otherNames': ['ACP-196'], 'description': 'acalabrutinib is a BTK inhibitor anticancer drug taken by mouth', 'armGroupLabels': ['Cohort 1 (R/R DLBCL)', 'Cohort 2 (R/R CLL)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '46526', 'city': 'Goshen', 'state': 'Indiana', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'Goshen Center for Cancer Care', 'geoPoint': {'lat': 41.58227, 'lon': -85.83444}}, {'zip': '45221', 'city': 'Cincinnati', 'state': 'Ohio', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'University of Cincinnati', 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'The Ohio State University Comprehensive Cancer Center', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'UT Southwestern Medical Center', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}, {'city': 'Adelaide', 'status': 'RECRUITING', 'country': 'Australia', 'facility': 'Royal Adelaide Hospital', 'geoPoint': {'lat': -34.92866, 'lon': 138.59863}}, {'city': 'Box Hill', 'status': 'RECRUITING', 'country': 'Australia', 'facility': 'Eastern Health - Box Hill Hospital', 'geoPoint': {'lat': -37.81887, 'lon': 145.12545}}, {'city': 'Geelong', 'status': 'RECRUITING', 'country': 'Australia', 'facility': 'Barwon Health', 'geoPoint': {'lat': -38.14711, 'lon': 144.36069}}, {'city': 'Perth', 'status': 'RECRUITING', 'country': 'Australia', 'facility': 'Royal Perth Hospital', 'geoPoint': {'lat': -31.95224, 'lon': 115.8614}}, {'city': 'Edegem', 'status': 'RECRUITING', 'country': 'Belgium', 'facility': 'Antwerp University Hospital (UZA)', 'geoPoint': {'lat': 51.15662, 'lon': 4.44504}}, {'city': 'Hasselt', 'status': 'RECRUITING', 'country': 'Belgium', 'facility': 'Jessa Ziekenhuis', 'geoPoint': {'lat': 50.93106, 'lon': 5.33781}}, {'city': 'Leuven', 'status': 'RECRUITING', 'country': 'Belgium', 'facility': 'University Hospital (UZ) Leuven', 'geoPoint': {'lat': 50.87959, 'lon': 4.70093}}, {'city': 'Nový Hradec Králové', 'status': 'RECRUITING', 'country': 'Czechia', 'facility': 'Fakultni Nemocnice Hradec Kralove', 'geoPoint': {'lat': 50.18185, 'lon': 15.85387}}, {'city': 'Ostrava', 'status': 'RECRUITING', 'country': 'Czechia', 'facility': 'Fakultni nemocnice Ostrava', 'geoPoint': {'lat': 49.83465, 'lon': 18.28204}}, {'city': 'Prague', 'status': 'RECRUITING', 'country': 'Czechia', 'facility': 'Vseobecna fakultni nemocnice v Praze', 'geoPoint': {'lat': 50.08804, 'lon': 14.42076}}, {'city': 'Nantes', 'status': 'RECRUITING', 'country': 'France', 'facility': 'CHU de Nantes - Hôtel-Dieu', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}, {'city': 'Rouen', 'status': 'RECRUITING', 'country': 'France', 'facility': 'Centre Henri Becquerel', 'geoPoint': {'lat': 49.44313, 'lon': 1.09932}}, {'city': 'Tours', 'status': 'RECRUITING', 'country': 'France', 'facility': 'CHRU de Tours - Hôpital Bretonneau', 'geoPoint': {'lat': 47.39484, 'lon': 0.70398}}, {'city': 'Aviano', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Centro Riferimento Oncologico - Aviano', 'geoPoint': {'lat': 46.07056, 'lon': 12.59472}}, {'city': 'Meldola', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori', 'geoPoint': {'lat': 44.12775, 'lon': 12.0626}}, {'city': 'Milan', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'ASST Grande Ospedale Metropolitano Niguarda', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'city': 'Milan', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'IRCCS Ospedale San Raffaele', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}, {'city': 'Pavia', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Fondazione IRCCS Policlinico San Matteo', 'geoPoint': {'lat': 45.19205, 'lon': 9.15917}}, {'city': 'Verona', 'status': 'RECRUITING', 'country': 'Italy', 'facility': 'Centro Ricerche Cliniche di Verona s.r.l.', 'geoPoint': {'lat': 45.43854, 'lon': 10.9938}}, {'city': 'Gdansk', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii', 'geoPoint': {'lat': 54.35227, 'lon': 18.64912}}, {'city': 'Gdansk', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii', 'geoPoint': {'lat': 54.35227, 'lon': 18.64912}}, {'city': 'Gliwice', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii', 'geoPoint': {'lat': 50.29761, 'lon': 18.67658}}, {'city': 'Krakow', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Pratia MCM Krakow', 'geoPoint': {'lat': 50.06143, 'lon': 19.93658}}, {'city': 'Krakow', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii', 'geoPoint': {'lat': 50.06143, 'lon': 19.93658}}, {'city': 'Wroclaw', 'status': 'RECRUITING', 'country': 'Poland', 'facility': 'Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu', 'geoPoint': {'lat': 51.10286, 'lon': 17.03006}}, {'city': 'Braga', 'status': 'RECRUITING', 'country': 'Portugal', 'facility': 'Hospital de Braga', 'geoPoint': {'lat': 41.5514, 'lon': -8.42311}}, {'city': 'Lisbon', 'status': 'RECRUITING', 'country': 'Portugal', 'facility': 'Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria', 'geoPoint': {'lat': 38.72509, 'lon': -9.1498}}, {'city': 'Lisbon', 'status': 'RECRUITING', 'country': 'Portugal', 'facility': 'Champalimaud Cancer Center', 'geoPoint': {'lat': 38.72509, 'lon': -9.1498}}, {'city': 'Porto', 'status': 'RECRUITING', 'country': 'Portugal', 'facility': 'Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE', 'geoPoint': {'lat': 41.1485, 'lon': -8.61097}}, {'city': 'Vila Nova de Gaia', 'status': 'RECRUITING', 'country': 'Portugal', 'facility': 'Centro Hospitalar de Vila Nova de Gaia/Espinho EPE', 'geoPoint': {'lat': 41.12401, 'lon': -8.61241}}, {'city': 'Goyang', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': 'National Cancer Center', 'geoPoint': {'lat': 36.21689, 'lon': 127.19731}}, {'city': 'Incheon', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': 'Gachon University Gil Medical Center', 'geoPoint': {'lat': 37.45646, 'lon': 126.70515}}, {'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': 'Samsung Medical Center', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': 'Seoul National University Hospital', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': "Seoul St. Mary's Hospital", 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Seoul', 'status': 'RECRUITING', 'country': 'South Korea', 'facility': 'Severance Hospital, Yonsei University Health System', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'city': 'Sankt Gallen', 'status': 'RECRUITING', 'country': 'Switzerland', 'facility': 'Kantonsspital St. Gallen', 'geoPoint': {'lat': 47.42391, 'lon': 9.37477}}, {'city': 'Leeds', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': "St James's University Hospital", 'geoPoint': {'lat': 53.79648, 'lon': -1.54785}}, {'city': 'London', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': "King's College Hospital", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'London', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': 'Royal Marsden Foundation Trust', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'Southampton', 'status': 'RECRUITING', 'country': 'United Kingdom', 'facility': 'University Hospital Southampton NHS Foundation Trust', 'geoPoint': {'lat': 50.90395, 'lon': -1.40428}}], 'centralContacts': [{'name': 'John Mei', 'role': 'CONTACT', 'email': 'jmei@kartosthera.com', 'phone': '650-542-0136'}, {'name': 'Michael Yee', 'role': 'CONTACT', 'email': 'myee@kartosthera.com', 'phone': '650-839-7361'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kartos Therapeutics, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}