Clinical trial NCT04502394: Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Chronic Lymphocytic Leukemia
Non Hodgkin Lymphoma
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma
Primary purpose: TREATMENT

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)


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Prior treatment with any MDM2 inhibitor
* Prior treatment with any BTK inhibitor

Primary outcomes:
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
measure: Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
timeFrame: 1 Year
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
Secondary outcomes:
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
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
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
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
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
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
measure: Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
timeFrame: 2 Years
Other outcomes:
Locations:
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Box Hill
country: Australia
facility: Eastern Health - Box Hill Hospital
city: Geelong
country: Australia
facility: Barwon Health
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Edegem
country: Belgium
facility: Antwerp University Hospital (UZA)
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: University Hospital (UZ) Leuven
city: Nový Hradec Králové
country: Czechia
facility: Fakultni Nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Tours
country: France
facility: CHRU de Tours - Hôpital Bretonneau
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - Aviano
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona s.r.l.
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
city: Gdańsk
country: Poland
facility: Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
city: Krakow
country: Poland
facility: Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
city: Lisbon
country: Portugal
facility: Champalimaud Cancer Center
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Marsden Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
References: