Clinical trial NCT04771130: A Study of BGB-11417 in Participants With Myeloid Malignancies
Official title: A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasm
Keywords: BGB-11417
Azacitidine
Posaconazole
AML
MDS
MDS/MPN
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2021-02-25
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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) .


Eligibility criteria: Key Inclusion Criteria:

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

   * AML, nonacute promyelocytic leukemia
   * MDS
   * MDS/MPN
2. Eastern Cooperative Oncology Group performance status of 0 to 2.
3. 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
4. Life expectancy of \> 12 weeks.
5. Ability to comply with the requirements of the study.

Key Exclusion Criteria:

1. A diagnosis of acute promyelocytic leukemia.
2. 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)
3. Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
4. Prior therapy with a B-cell lymphoma-2 inhibitor
5. Known central nervous system involvement by leukemia.

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

Primary outcomes:
measure: Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs)
measure: Part 1 And 2: Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate
timeFrame: Approximately 24 months
measure: Part 3 MDS Cohort: Modified Overall Response (mOR) Rate
timeFrame: Approximately 24 months
measure: 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
timeFrame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)
measure: Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Administered Alone and When Co-administered With Posaconazole
timeFrame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)
measure: 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
timeFrame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose)
measure: Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs
timeFrame: Cycle 2
measure: Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh)
timeFrame: Approximately 24 months
measure: Parts 1 And 2 MDS Cohort: mOR Rate
timeFrame: Approximately 24 months
measure: Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: Parts 1 And 2: Terminal Half-life (t1/2) Of Azacitidine When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: Parts 1 And 2: AUC From Time Zero To Time t (AUC0-t) Of Azacitidine When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: Parts 1 And 2: AUC From Time Zero To Infinity (AUC0-inf) Of Azacitidine When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: Parts 1 And 2: Apparent Total Clearance Of Azacitidine From Plasma (CL/F) When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: Parts 1 And 2: Apparent Volume Of Distribution (Vz/F) Of Azacitidine When Coadministered With BGB-11417
timeFrame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
measure: 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
timeFrame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose
measure: Parts 1 And 2: Steady-state Cmax (Cmax,ss) Of BGB-11417 When Coadministered With Azacitidine
timeFrame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose
measure: Parts 1 And 2: Steady-state Trough Plasma Concentration (Ctrough,ss) Of BGB-11417 When Coadministered With Azacitidine
timeFrame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose
measure: Parts 1 And 2: Steady-state Time To Maximum Observed Plasma Concentration (tmax,ss) Of BGB-11417 When Coadministered With Azacitidine
timeFrame: Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose
measure: Part 3: Number Of Participants Experiencing TEAEs
timeFrame: Approximately 24 months
measure: Part 3: Complete Response Rate
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: Overall Response Rate (ORR)
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: Duration Of Response (DOR)
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: Time To Response (TTR)
timeFrame: Approximately 24 months
measure: Part 3 Event-free Survival (EFS)
timeFrame: Approximately 24 months
measure: Part 3 Overall Survival (OS)
timeFrame: Approximately 24 months
measure: Part 3 AML Cohort: Number of Participants with Transfusion Independence
timeFrame: Approximately 24 months
measure: Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E)
timeFrame: Approximately 24 months
measure: Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P)
timeFrame: Approximately 24 months
measure: Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N)
timeFrame: Approximately 24 months
measure: Part 3 MDS Cohort: Number of participants with Transfusion Independence
timeFrame: Approximately 24 months
measure: Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose)
measure: Part 3 MDS cohort: Partial Hematologic Recovery CRh
timeFrame: Approximately 24 months
measure: Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery
timeFrame: Approximately 24 months
measure: Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417
timeFrame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose)
measure: Part 3 MDS (Treated with Monotherapy): Modified Overall Response
timeFrame: Approximately 24 months
measure: Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417
timeFrame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Pittsburgh
country: United States
facility: Upmc Hillman Cancer Center(Univ of Pittsburgh)
state: Pennsylvania
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Orange
country: Australia
facility: Orange Health Hospital
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The Second Peoples Hospital of Shenzhen
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Lille
country: France
facility: Hopital Claude Huriez Chu Lille
city: Nice
country: France
facility: Hopital Larchet
city: Paris
country: France
facility: Hopital Saint Louis
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig Aor
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
city: Milano
country: Italy
facility: Niguarda Cancer Center Division of Hematology
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital (Ccdhb)
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre
city: Greater Manchester
country: United Kingdom
facility: The Christie Hospital
Study officials:
References: