A Study of BGB-11417 in Participants With Myeloid Malignancies

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04771130
• Other study ID #: BGB-11417-103
• Secondary ID: 2021-003285-12
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 24, 2021
• Est. completion date: August 2025

Study information

• Verified date: October 2023
• Source: BeiGene
• Contact: BeiGene
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) .

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: August 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Prior malignancy within the past 2 years, except for curatively treated 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 or azacitidine except for participants who meet HMA-failure criteria

5. Known central nervous system involvement by leukemia. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm
• Myeloproliferative Disorders

Intervention

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

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincents Hospital Melbourne	Fitzroy	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
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	Orange Health Hospital	Orange	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	John Flynn Private Hospital	Tugun	Queensland
China	Peking University Peoples Hospital	Beijing	Beijing
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Guangdong Provincial Peoples Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	The Second Peoples Hospital of Shenzhen	Shenzhen	Guangdong
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan
Germany	Universitaetsklinikum Leipzig Aor	Leipzig
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul	Seoul Teugbyeolsi
New Zealand	North Shore Hospital	Takapuna
New Zealand	Wellington Regional Hospital (Ccdhb)	Wellington
Spain	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
United States	Maryland Oncology Hematology, Pa	Columbia	Maryland
United States	City of Hope National Medical Center	Duarte	California
United States	Md Anderson Cancer Center	Houston	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Upmc Hillman Cancer Center(Univ of Pittsburgh)	Pittsburgh	Pennsylvania
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia,  China,  Germany,  Korea, Republic of,  New Zealand,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs)		Approximately 24 months
Primary	Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate	CR plus CRh will be defined as the proportion 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.	Approximately 24 months
Primary	Part 3 MDS Cohort: Modified Overall Response (mOR) Rate	The mOR will be defined as the proportion 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).	Approximately 24 months
Primary	Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to the last quantifiable (AUC0-t) Of BGB-11417 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)
Primary	Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Coadministered With Posaconazole		Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)
Primary	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 Co-administered With Posaconazole		Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose)
Primary	Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs		Cycle 2
Primary	Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs		Approximately 24 months
Secondary	Parts 1 And 2 AML Cohort: CR Plus CRh Rate		Approximately 24 months
Secondary	Parts 1 And 2 MDS Cohort: mOR Rate		Approximately 24 months
Secondary	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
Secondary	Parts 1 And 2: 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
Secondary	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
Secondary	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
Secondary	Parts 1 And 2: Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs		Approximately 24 months
Secondary	Part 3: Complete Response	CR will be defined as the proportion 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.	Approximately 24 months
Secondary	Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate	CRi will be defined as the proportion of participants whose BOR is CRi.	Approximately 24 months
Secondary	Part 3 AML Cohort: Overall Response Rate (ORR)	The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.	Approximately 24 months
Secondary	Part 3 AML Cohort: Duration Of Response (DOR)	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.	Approximately 24 months
Secondary	Part 3 AML Cohort: Time To Response (TTR)	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.	Approximately 24 months
Secondary	Part 3 AML Cohort: Event-free Survival (EFS)	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.	Approximately 24 months
Secondary	Part 3 AML Cohort: Overall Survival (OS)	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.	Approximately 24 months
Secondary	Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs		Approximately 24 months
Secondary	Part 3 AML Cohort: Number of Participants with Transfusion Independence	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.	Approximately 24 months
Secondary	Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E)	The proportion of participants whose BOR is HI-E	Approximately 24 months
Secondary	Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P)	The proportion of participants whose BOR is HI-P	Approximately 24 months
Secondary	Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N)	The proportion of participants whose BOR is HI-N will be reported.	Approximately 24 months
Secondary	Part 3 MDS Cohort: Number of participants with Transfusion Independence	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.	Approximately 24 months
Secondary	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)
Secondary	Part 3 MDS cohort: Partial Hematologic Recovery CRh	Proportion of participants with partial hematologic recovery will be reported	Approximately 24 months
Secondary	Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery	Proportion of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.	Approximately 24 months
Secondary	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)
Secondary	Part 3 MDS (Treated with Monotherapy): Modified Overall Response	Proportion of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)	Approximately 24 months
Secondary	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)