Diffuse Large B Cell LymphomaPhase 1/2NCT04502394
Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
A Phase 1/2 study testing KRT-232 and acalabrutinib in people with Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia, run by Kartos Therapeutics, Inc. at 45 sites in 11 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma
- What is being tested?
- KRT-232 and acalabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 45 sitesin 11 countries
- Study dates
- 23 Feb 2021to Mar 2024
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Prior treatment with any MDM2 inhibitor
- Prior treatment with any BTK inhibitor
Trial locations and contacts
45 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
45 sites in 11 countries
Italy6 sites, 6 recruiting
- Recruiting
Centro Riferimento Oncologico - Aviano
Aviano
- Recruiting
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola
- Recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milan
- Recruiting
IRCCS Ospedale San Raffaele
Milan
- Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia
- Recruiting
Centro Ricerche Cliniche di Verona s.r.l.
Verona
Poland6 sites, 6 recruiting
- Recruiting
Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
Gdansk
- Recruiting
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
Gdansk
- Recruiting
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
Gliwice
- Recruiting
Pratia MCM Krakow
Krakow
- Recruiting
Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
Krakow
- Recruiting
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw
South Korea6 sites, 6 recruiting
- Recruiting
National Cancer Center
Goyang
- Recruiting
Gachon University Gil Medical Center
Incheon
- Recruiting
Samsung Medical Center
Seoul
- Recruiting
Seoul National University Hospital
Seoul
- Recruiting
Seoul St. Mary's Hospital
Seoul
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul
Portugal5 sites, 5 recruiting
- Recruiting
Hospital de Braga
Braga
- Recruiting
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
Lisbon
- Recruiting
Champalimaud Cancer Center
Lisbon
- Recruiting
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
Porto
- Recruiting
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
Vila Nova de Gaia
United States4 sites, 4 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45221
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Goshen Center for Cancer Care
Goshen, Indiana, 46526
Australia4 sites, 4 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide
- Recruiting
Eastern Health - Box Hill Hospital
Box Hill
- Recruiting
Barwon Health
Geelong
- Recruiting
Royal Perth Hospital
Perth
United Kingdom4 sites, 4 recruiting
- Recruiting
St James's University Hospital
Leeds
- Recruiting
King's College Hospital
London
- Recruiting
Royal Marsden Foundation Trust
London
- Recruiting
University Hospital Southampton NHS Foundation Trust
Southampton
Belgium3 sites, 3 recruiting
- Recruiting
Antwerp University Hospital (UZA)
Edegem
- Recruiting
Jessa Ziekenhuis
Hasselt
- Recruiting
University Hospital (UZ) Leuven
Leuven
Czechia3 sites, 3 recruiting
- Recruiting
Fakultni Nemocnice Hradec Kralove
Nový Hradec Králové
- Recruiting
Fakultni nemocnice Ostrava
Ostrava
- Recruiting
Vseobecna fakultni nemocnice v Praze
Prague
France3 sites, 3 recruiting
- Recruiting
CHU de Nantes - Hôtel-Dieu
Nantes
- Recruiting
Centre Henri Becquerel
Rouen
- Recruiting
CHRU de Tours - Hôpital Bretonneau
Tours
Switzerland1 site, 1 recruiting
- Recruiting
Kantonsspital St. Gallen
Sankt Gallen
About this study
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
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)
- Being tested
- KRT-232, acalabrutinib
- Keywords
- navtemadlin
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRT-232Drug
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
acalabrutinibDrug
Also called ACP-196
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (R/R DLBCL) | Experimental | 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. Receives: Drug: KRT-232; Drug: acalabrutinib |
| Cohort 2 (R/R CLL) | Experimental | 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. Receives: Drug: KRT-232; Drug: acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: 56 Days
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
Measured: 1 Year
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
Measured: 1 Year
Secondary outcomes (7)
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
Measured: 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
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
Measured: 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
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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).
Measured: 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
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
Measured: 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
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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.
Measured: 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
Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
Measured: 2 Years
Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
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
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start23 Feb 2021
- Primary completionOct 2022 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04502394
- Sponsor's protocol ID
- KRT-232-111
- Status last verified
- Aug 2022
- First submitted
- 27 Jul 2020
- Last updated
- 4 Aug 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No