Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
KRT-232-111
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B Cell Lymphoma 0 0
Chronic Lymphocytic Leukemia 0 0
Non Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
56 Days
Primary outcome [2] 0 0
Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
Timepoint [2] 0 0
1 Year
Primary outcome [3] 0 0
Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
Timepoint [3] 0 0
1 Year
Secondary outcome [1] 0 0
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
Timepoint [6] 0 0
2 Years
Secondary outcome [7] 0 0
Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
Timepoint [7] 0 0
2 Years

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any MDM2 inhibitor
* Prior treatment with any BTK inhibitor

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2024
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Eastern Health - Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Barwon Health - Geelong
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Box Hill
Recruitment postcode(s) [3] 0 0
- Geelong
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Indiana
Country [2] 0 0
United States of America
State/province [2] 0 0
Ohio
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Belgium
State/province [4] 0 0
Edegem
Country [5] 0 0
Belgium
State/province [5] 0 0
Hasselt
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Czechia
State/province [7] 0 0
Nový Hradec Králové
Country [8] 0 0
Czechia
State/province [8] 0 0
Ostrava
Country [9] 0 0
Czechia
State/province [9] 0 0
Prague
Country [10] 0 0
France
State/province [10] 0 0
Nantes
Country [11] 0 0
France
State/province [11] 0 0
Rouen
Country [12] 0 0
France
State/province [12] 0 0
Tours
Country [13] 0 0
Italy
State/province [13] 0 0
Aviano
Country [14] 0 0
Italy
State/province [14] 0 0
Meldola
Country [15] 0 0
Italy
State/province [15] 0 0
Milano
Country [16] 0 0
Italy
State/province [16] 0 0
Pavia
Country [17] 0 0
Italy
State/province [17] 0 0
Verona
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Goyang
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Incheon
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Poland
State/province [21] 0 0
Gdansk
Country [22] 0 0
Poland
State/province [22] 0 0
Gliwice
Country [23] 0 0
Poland
State/province [23] 0 0
Krakow
Country [24] 0 0
Poland
State/province [24] 0 0
Kraków
Country [25] 0 0
Poland
State/province [25] 0 0
Wroclaw
Country [26] 0 0
Portugal
State/province [26] 0 0
Braga
Country [27] 0 0
Portugal
State/province [27] 0 0
Lisboa
Country [28] 0 0
Portugal
State/province [28] 0 0
Lisbon
Country [29] 0 0
Portugal
State/province [29] 0 0
Porto
Country [30] 0 0
Portugal
State/province [30] 0 0
Vila Nova de Gaia
Country [31] 0 0
Switzerland
State/province [31] 0 0
Saint Gallen
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Leeds
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kartos Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

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)
Trial website
https://clinicaltrials.gov/study/NCT04502394
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Mei
Address 0 0
Country 0 0
Phone 0 0
650-542-0136
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04502394