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JOURNAL ONKOLOGIE – STUDIE

Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL

Rekrutierend

NCT-Nummer:
NCT04502394

Studienbeginn:
Februar 2021

Letztes Update:
04.08.2022

Wirkstoff:
KRT-232, Acalabrutinib

Indikation (Clinical Trials):
Lymphoma, Leukemia, Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Kartos Therapeutics, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 45)

Goshen Center for Cancer Care
46526 Goshen
United StatesRekrutierend» Google-Maps
University of Cincinnati
45221 Cincinnati
United StatesRekrutierend» Google-Maps
The Ohio State University Comprehensive Cancer Center
43210 Columbus
United StatesRekrutierend» Google-Maps
UT Southwestern Medical Center
75390 Dallas
United StatesRekrutierend» Google-Maps
Eastern Health - Box Hill Hospital
Box Hill
AustraliaRekrutierend» Google-Maps
Fakultni Nemocnice Hradec Kralove
Nový Hradec Králové
CzechiaRekrutierend» Google-Maps
Vseobecna fakultni nemocnice v Praze
Prague
CzechiaRekrutierend» Google-Maps
Centro Riferimento Oncologico - Aviano
Aviano
ItalyRekrutierend» Google-Maps
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola
ItalyRekrutierend» Google-Maps
ASST Grande Ospedale Metropolitano Niguarda
Milano
ItalyRekrutierend» Google-Maps
Fondazione IRCCS Policlinico San Matteo
Pavia
ItalyRekrutierend» Google-Maps
Centro Ricerche Cliniche di Verona s.r.l.
Verona
ItalyRekrutierend» Google-Maps
Gachon University Gil Medical Center
Incheon
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Seoul St. Mary's Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Severance Hospital, Yonsei University Health System
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
Gdansk
PolandRekrutierend» Google-Maps
Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
Gdańsk
PolandRekrutierend» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii
Gliwice
PolandRekrutierend» Google-Maps
Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii
Krakow
PolandRekrutierend» Google-Maps
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw
PolandRekrutierend» Google-Maps
Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
Lisboa
PortugalRekrutierend» Google-Maps
Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
Porto
PortugalRekrutierend» Google-Maps
Centro Hospitalar de Vila Nova de Gaia/Espinho EPE
Vila Nova de Gaia
PortugalRekrutierend» Google-Maps
St James's University Hospital
Leeds
United KingdomRekrutierend» Google-Maps
Royal Marsden Foundation Trust
London
United KingdomRekrutierend» Google-Maps
University Hospital Southampton NHS Foundation Trust
Southampton
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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)

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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 (Time Frame - 56 Days):
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.

2. Primary Objective Phase 2: Cohort 1: To determine the complete response (CR) (Time Frame - 1 Year):
Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.

3. Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL (Time Frame - 1 Year):
Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.

Secondary outcome:

1. Phase 1b Secondary Objective: Pharmacokinetic (PK) profile (Time Frame - 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):
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).

2. Phase 1b Secondary Objective: Pharmacokinetic (PK) profile (Time Frame - 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):
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).

3. Phase 1b Secondary Objective: Pharmacokinetic (PK) profile (Time Frame - 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):
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).

4. Phase 1b Secondary Objective: Pharmacokinetic (PK) profile (Time Frame - 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):
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.

5. Phase 1b Secondary Objective: Pharmacokinetic (PK) profile (Time Frame - 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):
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.

6. Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects. (Time Frame - 2 Years):
Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.

7. Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects (Time Frame - 2 Years):
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

Studien-Arme

  • 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.

Geprüfte Regime

  • KRT-232:
    KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
  • acalabrutinib (ACP-196):
    acalabrutinib is a BTK inhibitor anticancer drug taken by mouth

Quelle: ClinicalTrials.gov


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