A Study of BGB-11417 in Participants With Myeloid Malignancies

Официальное название

A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies

Обзор

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

Подробное описание

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Вмешательства

• Препарат BGB-11417
  Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.
• Препарат Azacitidine
  Intravenous or subcutaneous administration for 7 days.
• Препарат Posaconazole
  Oral administration for 8 days on second cycle only.
• Препарат BGB-11417
  Oral administration for 28 days on a 28-day cycle.
• Препарат BGB-11417
  Oral administration for 10, 14 or 21 days on a 28-day

Первичные конечные точки

• Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) [Срок оценки: Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs)]
• Part 1 And 2: Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Approximately 24 months]
• Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate [Срок оценки: Approximately 24 months]
• Part 3 MDS Cohort: Modified Overall Response (mOR) Rate [Срок оценки: Approximately 24 months]
• Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to the last quantifiable timepoint (t) (AUC0-t) Of BGB-11417 When Administered Alone and when Co-administered With Posaconazole [Срок оценки: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)]
• Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Administered Alone and When Co-administered With Posaconazole [Срок оценки: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)]
• Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to infinity (AUC0-infinity) Of BGB-11417 When Administered Alone and When Co-administered With Posaconazole [Срок оценки: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose)]
• Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs [Срок оценки: Cycle 2]
• Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs [Срок оценки: Approximately 24 months]

Вторичные конечные точки (12)

• Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh) [Срок оценки: Approximately 24 months]
• Parts 1 And 2 MDS Cohort: mOR Rate [Срок оценки: Approximately 24 months]
• Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: Terminal Half-life (t1/2) Of Azacitidine When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: AUC From Time Zero To Time t (AUC0-t) Of Azacitidine When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: AUC From Time Zero To Infinity (AUC0-inf) Of Azacitidine When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: Apparent Total Clearance Of Azacitidine From Plasma (CL/F) When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: Apparent Volume Of Distribution (Vz/F) Of Azacitidine When Coadministered With BGB-11417 [Срок оценки: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• Parts 1 And 2: Steady-state AUC From Time Zero To Time Of Last Measurable Concentration (AUClast,ss) Of BGB-11417 When Coadministered With Azacitidine [Срок оценки: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose]
• Parts 1 And 2: Steady-state Cmax (Cmax,ss) Of BGB-11417 When Coadministered With Azacitidine [Срок оценки: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose]
• Parts 1 And 2: Steady-state Trough Plasma Concentration (Ctrough,ss) Of BGB-11417 When Coadministered With Azacitidine [Срок оценки: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose]
• Parts 1 And 2: Steady-state Time To Maximum Observed Plasma Concentration (tmax,ss) Of BGB-11417 When Coadministered With Azacitidine [Срок оценки: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose]

Критерии участия

Критерии включения

• Confirmed diagnosis of one of the following by 2016 World Health Organization criteria:

• AML, nonacute promyelocytic leukemia
• MDS
• MDS/MPN
• Eastern Cooperative Oncology Group performance status of 0 to 2.
• Adequate organ function defined as:

• Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort)
• Adequate liver function
• Life expectancy of > 12 weeks.
• Ability to comply with the requirements of the study.

Критерии исключения

• A diagnosis of acute promyelocytic leukemia.
• History of prior malignancy, with the exception of either a history of MDS or MDS/MPN that has transformed to AML, or other prior malignancy that was treated with a full curative intent and no evidence of recurrence within the past 2 years (eg, localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer)
• Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
• Prior therapy with a B-cell lymphoma-2 inhibitor
• Known central nervous system involvement by leukemia.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

Китай · 12 центров

• Peking University Peoples Hospital — Пекин
• The First Hospital of Lanzhou University — Lanzhou
• Guangdong Provincial Peoples Hospital — Гуанчжоу
• Nanfang Hospital, Southern Medical University — Гуанчжоу
• The Second Peoples Hospital of Shenzhen — Шэньчжэнь
• Henan Cancer Hospital — Чжэнчжоу
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Ухань
• The First Affiliated Hospital of Soochow University — Сучжоу
• … и ещё 4 центра

Австралия · 11 центров

• Concord Repatriation General Hospital — Concord
• St George Hospital — Kogarah
• Orange Health Hospital — Orange
• Gold Coast University Hospital — Southport
• Monash Health — Clayton
• St Vincents Hospital Melbourne — Fitzroy
• Austin Health — Heidelberg
• The Alfred Hospital — Melbourne
• … и ещё 3 центра

США · 5 центров

• City of Hope National Medical Center — Duarte
• Tampa General Hospital — Tampa
• Upmc Hillman Cancer Center(Univ of Pittsburgh) — Pittsburgh
• Md Anderson Cancer Center — Houston
• Medical College of Wisconsin — Milwaukee

Испания · 4 центра

• Hospital de La Santa Creu I Sant Pau — Barcelona
• Hospital Universitario de Salamanca — Salamanca
• Hospital Universitario Virgen Del Rocio — Seville
• Hospital Universitari I Politecnic La Fe — Valencia

Франция · 3 центра

• Hopital Claude Huriez Chu Lille — Lille
• Hopital Larchet — Nice
• Hopital Saint Louis — Paris

Италия · 3 центра

• Policlinico Sorsola Malpighi, Aou Di Bologna — Bologna
• Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst — Meldola
• Niguarda Cancer Center Division of Hematology — Milan

Германия · 2 центра

• Universitaetsklinikum Leipzig Aor — Leipzig
• Universitaetsklinikum Ulm — Ulm

Новая Зеландия · 2 центра

• North Shore Hospital — Auckland
• Wellington Regional Hospital (Ccdhb) — Wellington

South Korea · 2 центра

• Samsung Medical Center — GangnamGu
• Severance Hospital Yonsei University Health System — SeodaemunGu

Великобритания · 2 центра

• Edinburgh Cancer Centre — Edinburgh
• The Christie Hospital — Greater Manchester

Идентификаторы

NCT: NCT04771130 · BGB-11417-103 · 2021-003285-12 · 2023-508881-14-00 · CTR20213416

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20213416 (платформа chinadrugtrials.org.cn)

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