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Trial record 1 of 1 for:    BGB-11417-103
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A Study of BGB-11417 in Participants With Myeloid Malignancies

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ClinicalTrials.gov Identifier: NCT04771130
Recruitment Status : Recruiting
First Posted : February 25, 2021
Last Update Posted : October 19, 2023
Sponsor:
Information provided by (Responsible Party):
BeiGene

Tracking Information
First Submitted Date  ICMJE February 23, 2021
First Posted Date  ICMJE February 25, 2021
Last Update Posted Date October 19, 2023
Actual Study Start Date  ICMJE May 24, 2021
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2022)
  • 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) ]
  • 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 ]
  • Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate [ Time Frame: 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.
  • Part 3 MDS Cohort: Modified Overall Response (mOR) Rate [ Time Frame: 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).
  • 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) ]
  • 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) ]
  • 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) ]
  • Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs [ Time Frame: Cycle 2 ]
  • Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs [ Time Frame: Approximately 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
  • 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) ]
  • Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Approximately 12 months ]
  • Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate [ Time Frame: 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.
  • Part 3 MDS Cohort: Modified Overall Response (mOR) Rate [ Time Frame: 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).
  • Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) Of BGB-11417 When Coadministered With Posaconazole [ Time Frame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose) ]
  • 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, 4, 6, 8, and 24 hours postdose) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2022)
  • Parts 1 And 2 AML Cohort: CR Plus CRh Rate [ Time Frame: Approximately 24 months ]
  • Parts 1 And 2 MDS Cohort: mOR Rate [ Time Frame: Approximately 24 months ]
  • Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417 [ Time Frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose ]
  • Parts 1 And 2: t1/2 Of Azacitidine When Coadministered With BGB-11417 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Drug From Plasma After Oral Administration (CL/F) Of Azacitidine When Coadministered With BGB-11417 [ Time Frame: 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 [ Time Frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose ]
  • 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs [ Time Frame: Approximately 24 months ]
  • Part 3: Complete Response [ Time Frame: 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.
  • Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate [ Time Frame: Approximately 24 months ]
    CRi will be defined as the proportion of participants whose BOR is CRi.
  • Part 3 AML Cohort: Overall Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 AML Cohort: Event-free Survival (EFS) [ Time Frame: 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 AML Cohort: Overall Survival (OS) [ Time Frame: 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 Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs [ Time Frame: Approximately 24 months ]
  • Part 3 AML Cohort: Number of Participants with Transfusion Independence [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose) ]
  • Part 3 MDS cohort: Partial Hematologic Recovery CRh [ Time Frame: Approximately 24 months ]
    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 [ Time Frame: Approximately 24 months ]
    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 [ Time Frame: 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 [ Time Frame: Approximately 24 months ]
    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 [ Time Frame: Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
  • Parts 1 And 2 AML Cohort: CR Plus CRh Rate [ Time Frame: Approximately 12 months ]
  • Parts 1 And 2 MDS Cohort: mOR Rate [ Time Frame: Approximately 12 months ]
  • Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Drug From Plasma After Oral Administration (CL/F) Of Azacitidine When Coadministered With BGB-11417 [ Time Frame: 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 [ Time Frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose ]
  • 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs [ Time Frame: Approximately 24 months ]
  • Part 3: CR [ Time Frame: 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.
  • Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate [ Time Frame: Approximately 24 months ]
    CRi will be defined as the proportion of participants whose BOR is CRi.
  • Part 3 AML Cohort: Overall Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 MDS Cohort: Proportion Of Participants With Hematological Improvement-erythroid (HI-E) [ Time Frame: Approximately 24 months ]
    The proportion of participants whose BOR is HI-E will be reported
  • Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P) [ Time Frame: Approximately 24 months ]
    The proportion of participants whose BOR is HI-P will be reported.
  • Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N) [ Time Frame: Approximately 24 months ]
    The proportion of participants whose BOR is HI-N will be reported.
  • Part 3 MDS Cohort: Transfusion Independence [ Time Frame: 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: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose) ]
  • Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs [ Time Frame: Approximately 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BGB-11417 in Participants With Myeloid Malignancies
Official Title  ICMJE A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm
Intervention  ICMJE
  • Drug: BGB-11417
    Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.
    Other Name: Sonrotoclax
  • Drug: Azacitidine
    Intravenous or subcutaneous administration for 7 days.
  • Drug: Posaconazole
    Oral administration for 8 days on second cycle only.
  • Drug: BGB-11417
    Oral administration for 28 days on a 28-day cycle.
  • Drug: BGB-11417
    Oral administration for 10 or 21 days on a 28-day
Study Arms  ICMJE
  • Experimental: Parts 1 and 2: AML Cohorts
    Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.
    Interventions:
    • Drug: BGB-11417
    • Drug: Azacitidine
  • Experimental: Parts 1 and 2: MDS Cohorts
    Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.
    Interventions:
    • Drug: Azacitidine
    • Drug: BGB-11417
  • 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.
    Interventions:
    • Drug: BGB-11417
    • Drug: Azacitidine
    • Drug: Posaconazole
  • 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.
    Intervention: Drug: BGB-11417
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2022)		 260
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2021)		 110
Estimated Study Completion Date  ICMJE August 2025
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: BeiGene 1.877.828.5568 clinicaltrials@beigene.com
Listed Location Countries  ICMJE Australia,   China,   Germany,   Korea, Republic of,   New Zealand,   Spain,   United States
Removed Location Countries France,   Italy,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT04771130
Other Study ID Numbers  ICMJE BGB-11417-103
2021-003285-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Current Responsible Party BeiGene
Original Responsible Party Same as current
Current Study Sponsor  ICMJE BeiGene
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account BeiGene
Verification Date October 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP