A Study of BGB-11417 in Participants With Myeloid Malignancies

Sponsor
BeiGene (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04771130
Collaborator
(none)
260
24
4
50.3
10.8
0.2

Study Details

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
260 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 24, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Aug 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Parts 1 and 2: AML Cohorts

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

Drug: BGB-11417
Oral administration for 10, 21 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Experimental: Parts 1 and 2: MDS Cohorts

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

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Drug: BGB-11417
Oral administration for 10 or 21 days on a 28-day

Experimental: Part 3: AML and MDS Cohorts

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.

Drug: BGB-11417
Oral administration for 10, 21 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Drug: Posaconazole
Oral administration for 8 days on second cycle only.

Experimental: Part 3: AML and MDS Cohort

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

Drug: BGB-11417
Oral administration for 28 days on a 28-day cycle.

Outcome Measures

Primary Outcome Measures

  1. 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)]

  2. Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs) [Approximately 24 months]

  3. 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 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.

  4. Part 3 MDS Cohort: Modified Overall Response (mOR) Rate [Approximately 24 months]

    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).

  5. 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)]

  6. 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)]

  7. 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)]

  8. Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs [Cycle 2]

  9. Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs [Approximately 24 months]

Secondary Outcome Measures

  1. Parts 1 And 2 AML Cohort: CR Plus CRh Rate [Approximately 24 months]

  2. Parts 1 And 2 MDS Cohort: mOR Rate [Approximately 24 months]

  3. 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]

  4. 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]

  5. 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]

  6. 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]

  7. 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]

  8. 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]

  9. 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]

  10. 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]

  11. 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]

  12. 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]

  13. Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs [Approximately 24 months]

  14. Part 3: Complete Response [Approximately 24 months]

    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.

  15. Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate [Approximately 24 months]

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

  16. 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.

  17. 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.

  18. 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.

  19. Part 3 AML Cohort: 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.

  20. Part 3 AML Cohort: 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.

  21. Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs [Approximately 24 months]

  22. 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.

  23. 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

  24. 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

  25. 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.

  26. Part 3 MDS 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.

  27. 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)]

  28. Part 3 MDS cohort: Partial Hematologic Recovery CRh [Approximately 24 months]

    Proportion of participants with partial hematologic recovery will be reported

  29. Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery [Approximately 24 months]

    Proportion of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.

  30. 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)]

  31. Part 3 MDS (Treated with Monotherapy): Modified Overall Response [Approximately 24 months]

    Proportion of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)

  32. 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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
  1. Confirmed diagnosis of one of the following by 2016 World Health Organization criteria:
  • AML, nonacute promyelocytic leukemia

  • MDS

  • MDS/MPN

  1. Eastern Cooperative Oncology Group performance status of 0 to 2.

  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

  1. Life expectancy of > 12 weeks.

  2. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 MD Anderson Cancer Center Houston Texas United States 77030
2 Pindara Private Hospital Benowa Australia 4217
3 Gold Coast University Hospital Gold Coast Australia 4215
4 Austin Hospital Heidelberg Australia 3084
5 The Alfred Hospital Melbourne Australia 3004
6 St. Vincent's Hospital Melbourne Melbourne Australia 3065
7 Monash Health Melbourne Australia 3168
8 Fiona Stanley Hospital Murdoch Australia 6150
9 One Clinical Research Nedlands Australia 6009
10 Orange Health Service Orange Australia 2800
11 Linear Clinical Research Perth Australia 6009
12 Concord Hospital Sydney Australia 2139
13 St. George Hospital Sydney Australia 2217
14 John Flynn Hospital Tugun Australia 4224
15 Peking University People's Hospital Beijing China 100044
16 West China Hospital Sichuan University Chengdu China 610041
17 Nanfang Hospital Guangzhou China 510515
18 The First Affiliated hospital of Nanchang University Nanchang China 330006
19 Union Hospital affiliated to Tongji Medical College of Huazhong University Wuhan China 430022
20 North Shore Hospital Auckland New Zealand 0620
21 Middlemore Hospital Auckland New Zealand 2025
22 Wellington Regional Hospital Wellington New Zealand 6021
23 Hospital Universitario Virgen del Rocío Sevilla Spain 41013
24 Hospital Politecnico Universitario La Fe Valencia Spain 46026

Sponsors and Collaborators

  • BeiGene

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
BeiGene
ClinicalTrials.gov Identifier:
NCT04771130
Other Study ID Numbers:
  • BGB-11417-103
  • 2021-003285-12
First Posted:
Feb 25, 2021
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by BeiGene
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 19, 2022