Back to results

A Study of BGB-11417 in Participants With Myeloid Malignancies

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BGB-11417

Azacitidine

Posaconazole

BGB-11417

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring BGB-11417, Azacitidine, Posaconazole, AML, MDS, MDS/MPN

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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 Exclusion Criteria:

A diagnosis of acute promyelocytic leukemia.
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.
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 or azacitidine except for participants who meet HMA-failure criteria
Known central nervous system involvement by leukemia.

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

Sites / Locations

City of Hope National Medical CenterRecruiting
Tampa General HospitalRecruiting
Maryland Oncology Hematology, PaRecruiting
Upmc Hillman Cancer Center(Univ of Pittsburgh)Recruiting
Md Anderson Cancer CenterRecruiting
Medical College of WisconsinRecruiting
Concord Repatriation General HospitalRecruiting
St George HospitalRecruiting
Orange Health HospitalRecruiting
Gold Coast University HospitalRecruiting
John Flynn Private HospitalRecruiting
Monash HealthRecruiting
St Vincents Hospital MelbourneRecruiting
Austin HealthRecruiting
The Alfred HospitalRecruiting
Fiona Stanley HospitalRecruiting
Linear Clinical ResearchRecruiting
One Clinical ResearchRecruiting
Peking University Peoples HospitalRecruiting
The First Hospital of Lanzhou UniversityRecruiting
Guangdong Provincial Peoples HospitalRecruiting
Nanfang Hospital of Southern Medical UniversityRecruiting
The Second Peoples Hospital of ShenzhenRecruiting
Henan Cancer HospitalRecruiting
Union Hospital of Tongji Medical College, Huazhong University of Science and TechnologyRecruiting
The First Affiliated Hospital of Soochow UniversityRecruiting
The First Affiliated Hospital of Nanchang University Branch DonghuRecruiting
West China Hospital, Sichuan UniversityRecruiting
Tianjin Medical University Cancer Institute and HospitalRecruiting
The First Affiliated Hospital, Zhejiang University School of MedicineRecruiting
Universitaetsklinikum Leipzig AorRecruiting
Seoul National University HospitalRecruiting
Severance Hospital Yonsei University Health SystemRecruiting
Asan Medical CenterRecruiting
Samsung Medical CenterRecruiting
North Shore HospitalRecruiting
Wellington Regional Hospital (Ccdhb)Recruiting
Hospital de La Santa Creu I Sant PauRecruiting
Hospital Universitario de SalamancaRecruiting
Hospital Universitario Virgen Del RocioRecruiting
Hospital Universitari I Politecnic La FeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Parts 1 and 2: AML Cohorts

Parts 1 and 2: MDS Cohorts

Part 3: AML and MDS Cohorts

Part 3: AML and MDS Cohort

Arm Description

Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.

Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.

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.

Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle.

Outcomes

Primary Outcome Measures

Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs)

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.

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).

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

Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Coadministered With Posaconazole

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

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs

Secondary Outcome Measures

Parts 1 And 2 AML Cohort: CR Plus CRh Rate

Parts 1 And 2 MDS Cohort: mOR Rate

Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417

Parts 1 And 2: t1/2 Of Azacitidine When Coadministered With BGB-11417

Parts 1 And 2: AUC From Time Zero To Time t (AUC0-t) Of Azacitidine When Coadministered With BGB-11417

Parts 1 And 2: AUC From Time Zero To Infinity (AUC0-inf) Of Azacitidine When Coadministered With BGB-11417

Parts 1 And 2: Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of Azacitidine When Coadministered With BGB-11417

Parts 1 And 2: Apparent Volume Of Distribution (Vz/F) Of Azacitidine When Coadministered With BGB-11417

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

Parts 1 And 2: Steady-state Cmax (Cmax,ss) Of BGB-11417 When Coadministered With Azacitidine

Parts 1 And 2: Steady-state Trough Plasma Concentration (Ctrough,ss) Of BGB-11417 When Coadministered With Azacitidine

Parts 1 And 2: Steady-state Time To Maximum Observed Plasma Concentration (tmax,ss) Of BGB-11417 When Coadministered With Azacitidine

Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs

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.

Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate

CRi will be defined as the proportion of participants whose BOR is CRi.

Part 3 AML Cohort: Overall Response Rate (ORR)

The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.

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.

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.

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.

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.

Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs

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.

Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E)

The proportion of participants whose BOR is HI-E

Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P)

The proportion of participants whose BOR is HI-P

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.

Part 3 MDS Cohort: Number of participants with Transfusion Independence

Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine

Part 3 MDS cohort: Partial Hematologic Recovery CRh

Proportion of participants with partial hematologic recovery will be reported

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.

Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417

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)

Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417

Full Information

NCT ID

NCT04771130

First Posted

February 23, 2021

Last Updated

October 18, 2023

Sponsor

BeiGene

1. Study Identification

Unique Protocol Identification Number

NCT04771130

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 24, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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) .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm

Keywords

BGB-11417, Azacitidine, Posaconazole, AML, MDS, MDS/MPN

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Parts 1 and 2: AML Cohorts

Arm Type

Experimental

Arm Description

Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.

Arm Title

Parts 1 and 2: MDS Cohorts

Arm Type

Experimental

Arm Description

Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.

Arm Title

Part 3: AML and MDS Cohorts

Arm Type

Experimental

Arm Description

Arm Title

Part 3: AML and MDS Cohort

Arm Type

Experimental

Arm Description

Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

BGB-11417

Other Intervention Name(s)

Sonrotoclax

Intervention Description

Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Intervention Description

Intravenous or subcutaneous administration for 7 days.

Intervention Type

Drug

Intervention Name(s)

Posaconazole

Intervention Description

Oral administration for 8 days on second cycle only.

Intervention Type

Drug

Intervention Name(s)

BGB-11417

Intervention Description

Oral administration for 28 days on a 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

BGB-11417

Intervention Description

Oral administration for 10 or 21 days on a 28-day

Primary Outcome Measure Information:

Title

Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)

Time Frame

Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs)

Title

Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs)

Time Frame

Approximately 24 months

Title

Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate

Description

Time Frame

Approximately 24 months

Title

Part 3 MDS Cohort: Modified Overall Response (mOR) Rate

Description

Time Frame

Approximately 24 months

Title

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

Time Frame

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)

Title

Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Coadministered With Posaconazole

Time Frame

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose)

Title

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

Time Frame

Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose)

Title

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs

Time Frame

Cycle 2

Title

Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs

Time Frame

Approximately 24 months

Secondary Outcome Measure Information:

Title

Parts 1 And 2 AML Cohort: CR Plus CRh Rate

Time Frame

Approximately 24 months

Title

Parts 1 And 2 MDS Cohort: mOR Rate

Time Frame

Approximately 24 months

Title

Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417

Time Frame