ICP-248 in Combination With Azacitidine for the Treatment in Patients With Myeloid Malignancies

Официальное название

A Phase 1 Study of ICP-248 in Combination With Azacitidine for the Treatment in Patients With Myeloid Malignancies.

Обзор

Evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ICP-248 in combination with azacitidine in patients with acute myelogenous leukemia and Myelodysplastic Syndromes.

Вмешательства

• Препарат ICP-248
  Eligible patients will receive ICP-248 orally as per the protocol，once daily for every 28 days as one treatment cycle
• Препарат Azacitidine
  Eligible patients will receive azacitidine subcutaneously or intravenously as per the protocol，once daily on days 1-7 of each 28-day cycle.

Первичные конечные точки

• Incidence, type, and severity of dose-limiting toxicity (DLT). [Срок оценки: 2.5 years]
• Recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD). [Срок оценки: 2.5 years]
• The incidence, nature, and severity of adverse events (AEs) as assessed per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) criteria. [Срок оценки: 2.5 years]
• AML cohort:Composite complete remission rate by Investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• AML cohort：Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• MDS cohort：mOR rate, including CR, mCR, and PR, assessed by Investigator at any time point during the study per revised IWG 2006 MDS Criteria. [Срок оценки: 2.5 years]

Вторичные конечные точки (12)

• AML cohort：Composite complete remission rate: The proportion of subjects with complete remission (CR) and CR with incomplete hematologic recovery (CRi) by Investigator per European Leukemia Net (ELN) 2017 criteria. [Срок оценки: 2.5 years]
• AML cohort：Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• The incidence, nature, and severity of adverse events (AEs) as assessed per NCI-CTCAE v5.0 criteria. [Срок оценки: 2.5 years]
• Maximum concentration (Cmax)of ICP-248. [Срок оценки: 2.5 years]
• Area under the curve (AUC) of ICP-248. [Срок оценки: 2.5 years]
• Time of maximum observed plasma(Tmax)of ICP-248. [Срок оценки: 2.5 years]
• Trough concentration(Ctrough) of ICP-248. [Срок оценки: 2.5 years]
• Apparent clearance (CL/F) of ICP-248. [Срок оценки: 2.5 years]
• AML cohort：Partial Response (PR) by investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• AML cohort：Overall survival (OS) by investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• AML cohort：Duration of Response (DOR) by investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]
• AML cohort：Event-free Survival (EFS) by investigator per ELN 2017 criteria. [Срок оценки: 2.5 years]

Критерии участия

Критерии включения

Eligible subjects must meet all of the following criteria:

• Subject must have confirmation of diagnosis of AML (except for acute promyelocytic leukemia \[APL\]) or MDS per 2016 World Health Organization (WHO) criteria.
• For AML (except for APL) cohort:

• Previously treated relapsed/refractory AML subjects
• Treatment-naïve AML subjects should be: ≥60 years of age OR ≥18 years and <60 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy
• For MDS cohort: Adult TN MDS and R/R MDS: revised International Prognostic Scoring System (IPSS-R) score > 3 and bone marrow blasts ≥ 5%.
• Subject must have a projected life expectancy of at least 12 weeks.
• Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft-Gault formula.
• Subject must have adequate liver function

Критерии исключения

• R/R AML or R/R MDS with no response or intolerance to post azacitidine or BCL-2i.
• Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) .
• Subject has known central nervous system (CNS) leukemia.
• Suggest patients with active hepatitis B or C virus infection
• History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
• Subjects have another active malignancy within the past 2 years before study entry, except for curatively treated.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 14 центров

• Anhui Provincial Hospita — Хэфэй
• Peking University People's Hospital — Пекин
• The First Affiliated Hospital of Chongqing Medical University — Чунцин
• Guangdong Provincial People's Hospital — Гуанчжоу
• Nanfang Hospital Southern Medical University — Гуанчжоу
• Henan Cancer Hospital — Чжэнчжоу
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Ухань
• The First Affiliated Hospital of Soochow University — Сучжоу
• … и ещё 6 центров

США · 2 центра

• Yale University, Yale Cancer Center — New Haven
• NYU Langone Health — New York

Австралия · 2 центра

• St Vincent's Hospital — Sydney
• Royal Perth Hospital — Perth

Идентификаторы

NCT: NCT06656494 · ICP-CL-01205

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗