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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04502394
Registration number
NCT04502394
Ethics application status
Date submitted
27/07/2020
Date registered
6/08/2020
Date last updated
4/08/2022
Titles & IDs
Public title
Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL
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Scientific 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
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Secondary ID [1]
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KRT-232-111
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B Cell Lymphoma
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Chronic Lymphocytic Leukemia
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Non Hodgkin Lymphoma
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Condition category
Condition code
Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - KRT-232
Treatment: Drugs - acalabrutinib
Experimental: Cohort 1 (R/R DLBCL) - 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.
Experimental: Cohort 2 (R/R CLL) - 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.
Treatment: Drugs: KRT-232
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
Treatment: Drugs: acalabrutinib
acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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
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Assessment method [1]
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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.
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Timepoint [1]
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56 Days
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Primary outcome [2]
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Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
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Assessment method [2]
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Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
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Timepoint [2]
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1 Year
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Primary outcome [3]
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Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
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Assessment method [3]
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Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
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Timepoint [3]
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1 Year
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Secondary outcome [1]
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Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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Assessment method [1]
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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).
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Timepoint [1]
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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
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Secondary outcome [2]
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Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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Assessment method [2]
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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).
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Timepoint [2]
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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
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Secondary outcome [3]
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Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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Assessment method [3]
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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).
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Timepoint [3]
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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
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Secondary outcome [4]
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Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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Assessment method [4]
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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.
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Timepoint [4]
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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
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Secondary outcome [5]
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Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
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Assessment method [5]
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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.
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Timepoint [5]
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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
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Secondary outcome [6]
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Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
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Assessment method [6]
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Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
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Timepoint [6]
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2 Years
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Secondary outcome [7]
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Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
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Assessment method [7]
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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
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Timepoint [7]
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2 Years
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Prior treatment with any MDM2 inhibitor
- Prior treatment with any BTK inhibitor
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
23/02/2021
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Date of last participant enrolment
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Actual
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Date of last data collection
Anticipated
1/03/2024
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Actual
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Sample size
Target
84
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [2]
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Eastern Health - Box Hill Hospital - Box Hill
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Recruitment hospital [3]
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Barwon Health - Geelong
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Recruitment hospital [4]
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Royal Perth Hospital - Perth
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Recruitment postcode(s) [1]
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- Adelaide
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Recruitment postcode(s) [2]
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- Box Hill
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Recruitment postcode(s) [3]
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- Geelong
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Recruitment postcode(s) [4]
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- Perth
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Recruitment outside Australia
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United States of America
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Indiana
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United States of America
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Ohio
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United States of America
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Texas
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Belgium
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Edegem
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Belgium
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Hasselt
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Belgium
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Leuven
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Czechia
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Nový Hradec Králové
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Czechia
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Ostrava
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Czechia
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Prague
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France
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Nantes
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France
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Rouen
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France
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Tours
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Italy
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Aviano
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Italy
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Meldola
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Italy
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Milano
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Italy
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Pavia
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Italy
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Verona
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Korea, Republic of
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Goyang
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Gdansk
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Gliwice
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Krakow
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Kraków
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Wroclaw
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Portugal
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Braga
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Portugal
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Lisboa
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Portugal
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Lisbon
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Portugal
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Porto
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Portugal
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Vila Nova de Gaia
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Switzerland
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Saint Gallen
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Kartos Therapeutics, Inc.
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Address
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Ethics approval
Ethics application status
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Summary
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)
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04502394
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Email
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Contact person for public queries
Name
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John Mei
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Address
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Phone
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650-542-0136
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04502394
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