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

Официальное название

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

Обзор

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)

Вмешательства

• Препарат KRT-232
  KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
• Препарат acalabrutinib
  acalabrutinib is a BTK inhibitor anticancer drug taken by mouth

Первичные конечные точки

• 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 [Срок оценки: 56 Days]
• Primary Objective Phase 2: Cohort 1: To determine the complete response (CR) [Срок оценки: 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 [Срок оценки: 1 Year]

Вторичные конечные точки (7)

• Phase 1b Secondary Objective: Pharmacokinetic (PK) profile [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: 2 Years]
• Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects [Срок оценки: 2 Years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Prior treatment with any MDM2 inhibitor
• Prior treatment with any BTK inhibitor

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 6 центров

• Centro Riferimento Oncologico - Aviano — Aviano
• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori — Meldola
• ASST Grande Ospedale Metropolitano Niguarda — Milan
• IRCCS Ospedale San Raffaele — Milan
• Fondazione IRCCS Policlinico San Matteo — Pavia
• Centro Ricerche Cliniche di Verona s.r.l. — Verona

Польша · 6 центров

• Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii — Gdansk
• Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii — Gdansk
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Od — Gliwice
• Pratia MCM Krakow — Krakow
• Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii — Krakow
• Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu — Wroclaw

South Korea · 6 центров

• National Cancer Center — Goyang
• Gachon University Gil Medical Center — Incheon
• Samsung Medical Center — Seoul
• Seoul National University Hospital — Seoul
• Seoul St. Mary's Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul

Португалия · 5 центров

• Hospital de Braga — Braga
• Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria — Lisbon
• Champalimaud Cancer Center — Lisbon
• Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE — Porto
• Centro Hospitalar de Vila Nova de Gaia/Espinho EPE — Vila Nova de Gaia

США · 4 центра

• Goshen Center for Cancer Care — Goshen
• University of Cincinnati — Cincinnati
• The Ohio State University Comprehensive Cancer Center — Columbus
• UT Southwestern Medical Center — Dallas

Австралия · 4 центра

• Royal Adelaide Hospital — Adelaide
• Eastern Health - Box Hill Hospital — Box Hill
• Barwon Health — Geelong
• Royal Perth Hospital — Perth

Великобритания · 4 центра

• St James's University Hospital — Leeds
• King's College Hospital — London
• Royal Marsden Foundation Trust — London
• University Hospital Southampton NHS Foundation Trust — Southampton

Бельгия · 3 центра

• Antwerp University Hospital (UZA) — Edegem
• Jessa Ziekenhuis — Hasselt
• University Hospital (UZ) Leuven — Leuven

Чехия · 3 центра

• Fakultni Nemocnice Hradec Kralove — Nový Hradec Králové
• Fakultni nemocnice Ostrava — Ostrava
• Vseobecna fakultni nemocnice v Praze — Prague

Франция · 3 центра

• CHU de Nantes - Hôtel-Dieu — Nantes
• Centre Henri Becquerel — Rouen
• CHRU de Tours - Hôpital Bretonneau — Tours

Швейцария · 1 центр

• Kantonsspital St. Gallen — Sankt Gallen

Идентификаторы

NCT: NCT04502394 · KRT-232-111

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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