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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 : June 10, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasm Drug: BGB-11417 Drug: Azacitidine Drug: Posaconazole Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 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
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : June 2024


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 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Experimental: Experimental: Parts 1 and 2: MDS Cohorts
Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.
Drug: BGB-11417
Oral administration for 10 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Experimental: Part 3: AML Cohort
Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle (or 10-day cycle as determined after Parts 1 and 2). 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 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.

Drug: Posaconazole
Oral administration for 10 days on second cycle only.

Experimental: Part 3: MDS Cohort
Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.
Drug: BGB-11417
Oral administration for 10 or 28 days on a 28-day cycle.

Drug: Azacitidine
Intravenous or subcutaneous administration for 7 days.




Primary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. 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.

  4. 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).

  5. 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) ]
  6. 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) ]

Secondary Outcome Measures :
  1. Parts 1 And 2 AML Cohort: CR Plus CRh Rate [ Time Frame: Approximately 12 months ]
  2. Parts 1 And 2 MDS Cohort: mOR Rate [ Time Frame: Approximately 12 months ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs [ Time Frame: Approximately 24 months ]
  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  21. 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.

  22. 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.

  23. 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.

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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Confirmed diagnosis of one of the following by 2016 World Health Organization criteria:

    • AML, nonacute promyelocytic leukemia
    • MDS
    • MDS/MPN For treatment naïve AML, must be unfit for intensive chemotherapy
  2. Eastern Cooperative Oncology Group performance status of 0 to 2.
  3. Adequate organ function defined as:

    • Creatinine clearance ≥ 45 milliliters/minute (mL/min) (or between 30 and 45 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.
  5. Known central nervous system involvement by leukemia.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04771130


Contacts
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Contact: BeiGene 1.877.828.5568 clinicaltrials@beigene.com

Locations
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Sponsors and Collaborators
BeiGene
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04771130    
Other Study ID Numbers: BGB-11417-103
First Posted: February 25, 2021    Key Record Dates
Last Update Posted: June 10, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by BeiGene:
BGB-11417
Azacitidine
Posaconazole
AML
MDS
MDS/MPN
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Posaconazole
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs