Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
- Conditions
- Chronic Lymphocytic LeukemiaNon Hodgkin LymphomaDiffuse Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT04502394
- Lead Sponsor
- Kartos Therapeutics, Inc.
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 84
- 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
- Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior line of treatment
- ECOG 0 to 2
- Adequate hematologic, hepatic, and renal functions.
- Prior treatment with any MDM2 inhibitor
- Prior treatment with any BTK inhibitor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 (R/R DLBCL) KRT-232 KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 2 (R/R CLL) KRT-232 KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 2 (R/R CLL) acalabrutinib KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle. Cohort 1 (R/R DLBCL) acalabrutinib KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle. Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
- Primary Outcome Measures
Name Time Method 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 56 Days 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.
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR) 1 Year Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL 1 Year Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
- Secondary Outcome Measures
Name Time Method Phase 1b Secondary Objective: Pharmacokinetic (PK) profile 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 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.
Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects. 2 Years Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects 2 Years 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
Trial Locations
- Locations (45)
Seoul St. Mary's Hospital
๐ฐ๐ทSeoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
๐ต๐ฑGdansk, Poland
Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
๐ต๐ฑGdaลsk, Poland
Champalimaud Cancer Center
๐ต๐นLisbon, Portugal
Severance Hospital, Yonsei University Health System
๐ฐ๐ทSeoul, Korea, Republic of
Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
๐ต๐ฑKrakow, Poland
Pratia MCM Krakow
๐ต๐ฑKrakรณw, Poland
Fondazione IRCCS Policlinico San Matteo
๐ฎ๐นPavia, Italy
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
๐ต๐นLisboa, Portugal
Samsung Medical Center
๐ฐ๐ทSeoul, Korea, Republic of
Antwerp University Hospital (UZA)
๐ง๐ชEdegem, Belgium
Jessa Ziekenhuis
๐ง๐ชHasselt, Belgium
University Hospital (UZ) Leuven
๐ง๐ชLeuven, Belgium
CHU de Nantes - Hรดtel-Dieu
๐ซ๐ทNantes, France
Centre Henri Becquerel
๐ซ๐ทRouen, France
CHRU de Tours - Hรดpital Bretonneau
๐ซ๐ทTours, France
Fakultni nemocnice Ostrava
๐จ๐ฟOstrava, Czechia
Fakultni Nemocnice Hradec Kralove
๐จ๐ฟNovรฝ Hradec Krรกlovรฉ, Czechia
Royal Perth Hospital
๐ฆ๐บPerth, Australia
Centro Riferimento Oncologico - Aviano
๐ฎ๐นAviano, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
๐ฎ๐นMeldola, Italy
ASST Grande Ospedale Metropolitano Niguarda
๐ฎ๐นMilano, Italy
Royal Marsden Foundation Trust
๐ฌ๐งLondon, United Kingdom
IRCCS Ospedale San Raffaele
๐ฎ๐นMilano, Italy
Gachon University Gil Medical Center
๐ฐ๐ทIncheon, Korea, Republic of
Centro Ricerche Cliniche di Verona s.r.l.
๐ฎ๐นVerona, Italy
National Cancer Center
๐ฐ๐ทGoyang, Korea, Republic of
University Hospital Southampton NHS Foundation Trust
๐ฌ๐งSouthampton, United Kingdom
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
๐ต๐ฑGliwice, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
๐ต๐ฑWroclaw, Poland
Hospital de Braga
๐ต๐นBraga, Portugal
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
๐ต๐นVila Nova de Gaia, Portugal
Kantonsspital St. Gallen
๐จ๐ญSaint Gallen, Switzerland
St James's University Hospital
๐ฌ๐งLeeds, United Kingdom
Vseobecna fakultni nemocnice v Praze
๐จ๐ฟPrague, Czechia
Goshen Center for Cancer Care
๐บ๐ธGoshen, Indiana, United States
University of Cincinnati
๐บ๐ธCincinnati, Ohio, United States
The Ohio State University Comprehensive Cancer Center
๐บ๐ธColumbus, Ohio, United States
Eastern Health - Box Hill Hospital
๐ฆ๐บBox Hill, Australia
UT Southwestern Medical Center
๐บ๐ธDallas, Texas, United States
Royal Adelaide Hospital
๐ฆ๐บAdelaide, Australia
Barwon Health
๐ฆ๐บGeelong, Australia
Seoul National University Hospital
๐ฐ๐ทSeoul, Korea, Republic of
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
๐ต๐นPorto, Portugal
King's College Hospital
๐ฌ๐งLondon, United Kingdom