A Study of BGB-11417 in Participants With Myeloid Malignancies
- Conditions
- Acute Myeloid LeukemiaMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative Neoplasm
- Interventions
- Registration Number
- NCT04771130
- Lead Sponsor
- BeiGene
- 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) .
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 260
-
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.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 3: AML and MDS Cohort BGB-11417 Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle. Parts 1 and 2: AML Cohorts BGB-11417 Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle. Parts 1 and 2: AML Cohorts Azacitidine Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle. Parts 1 and 2: MDS Cohorts Azacitidine Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle. Parts 1 and 2: MDS Cohorts BGB-11417 Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle. Part 3: AML and MDS Cohorts BGB-11417 Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole. Part 3: AML and MDS Cohorts Azacitidine Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole. Part 3: AML and MDS Cohorts Posaconazole Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole.
- Primary Outcome Measures
Name Time Method Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) 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) Approximately 24 months Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate Approximately 24 months CR plus CRh will be defined as the percentage of participants whose best overall response (BOR) is CR plus CRh. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.
Part 3 MDS Cohort: Modified Overall Response (mOR) Rate Approximately 24 months The mOR will be defined as the percentage of participants whose BOR is achieving CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study for myelodysplastic/myeloproliferative neoplasm (MDS/MPN).
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 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 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 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 Cycle 2 Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs Approximately 24 months
- Secondary Outcome Measures
Name Time Method Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417 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 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 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 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 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 Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh) Approximately 24 months Parts 1 And 2 MDS Cohort: mOR Rate Approximately 24 months 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 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 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 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 Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose Part 3: Number Of Participants Experiencing TEAEs Approximately 24 months Part 3: Complete Response Rate Approximately 24 months CR will be defined as the percentage of participants whose BOR is CR. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.
Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate Approximately 24 months CRi will be defined as the percentage of participants whose BOR is CRi.
Part 3 AML Cohort: Overall Response Rate (ORR) Approximately 24 months The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.
Part 3 AML Cohort: Duration Of Response (DOR) Approximately 24 months DOR will be defined as the time from the first response to disease progression documented after treatment initiation or death, whichever occurs first. DOR will include CR, CR plus CRi, overall response (OR), and CR plus CRh.
Part 3 AML Cohort: Time To Response (TTR) Approximately 24 months TTR will be defined as the time from treatment initiation to the first documented response and will include CR, CR plus CRi, OR, and CR plus CRh.
Part 3 Event-free Survival (EFS) Approximately 24 months EFS will be defined as the time from treatment initiation to disease progression, treatment failure, relapse (hematologic relapse for AML) for those who have treatment success, or death due to any cause, whichever happens first.
Part 3 Overall Survival (OS) Approximately 24 months OS will be defined as the time from treatment initiation to death. OS will be analyzed using the same methods as the EFS analysis except for the censoring rules.
Part 3 AML Cohort: Number of Participants with Transfusion Independence Approximately 24 months Transfusion independence will be defined as the proportion of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.
Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E) Approximately 24 months The proportion of participants whose BOR is HI-E
Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P) Approximately 24 months The proportion of participants whose BOR is HI-P
Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N) Approximately 24 months The proportion of participants whose BOR is HI-N will be reported.
Part 3 MDS Cohort: Number of participants with Transfusion Independence Approximately 24 months Transfusion independence will be defined as the percentage of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.
Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose) Part 3 MDS cohort: Partial Hematologic Recovery CRh Approximately 24 months Percentage of participants with partial hematologic recovery will be reported
Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery Approximately 24 months Percentage of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.
Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417 Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose) Part 3 MDS (Treated with Monotherapy): Modified Overall Response Approximately 24 months Percentage of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)
Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417 Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose)
Trial Locations
- Locations (49)
Hopital Saint Louis
🇫🇷Paris, France
Universitaetsklinikum Leipzig Aor
🇩🇪Leipzig, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Policlinico Sorsola Malpighi, Aou Di Bologna
🇮🇹Bologna, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
🇮🇹Meldola, Italy
Niguarda Cancer Center Division of Hematology
🇮🇹Milano, Italy
Hopital Larchet
🇫🇷Nice, France
Hopital Claude Huriez Chu Lille
🇫🇷Lille, France
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Upmc Hillman Cancer Center(Univ of Pittsburgh)
🇺🇸Pittsburgh, Pennsylvania, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Orange Health Hospital
🇦🇺Orange, New South Wales, Australia
Monash Health
🇦🇺Clayton, Victoria, Australia
St Vincents Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
One Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Peking University Peoples Hospital
🇨🇳Beijing, Beijing, China
The First Hospital of Lanzhou University
🇨🇳Lanzhou, Gansu, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Second Peoples Hospital of Shenzhen
🇨🇳Shenzhen, Guangdong, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Samsung Medical Center
🇰🇷GangnamGu, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
North Shore Hospital
🇳🇿Auckland, New Zealand
Aotearoa Clinical Trials
🇳🇿Auckland, New Zealand
Wellington Regional Hospital (Ccdhb)
🇳🇿Wellington, New Zealand
Hospital de La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari I Politecnic La Fe
🇪🇸Valencia, Spain
Edinburgh Cancer Centre
🇬🇧Edinburgh, United Kingdom
The Christie Hospital
🇬🇧Greater Manchester, United Kingdom