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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
Trial website
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
jmei@kartosthera.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04502394