Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm
Conditions
Keywords
BGB-11417, Azacitidine, Posaconazole, AML, MDS, MDS/MPN
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) .
Interventions
DRUGBGB-11417
Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.
DRUGAzacitidine
Intravenous or subcutaneous administration for 7 days.
DRUGPosaconazole
Oral administration for 8 days on second cycle only.
Sponsors
BeiGene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 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. History of prior malignancy, with the exception of either a history of MDS or MDS/MPN that has transformed to AML, or other prior malignancy that was treated with a full curative intent and no evidence of recurrence within the past 2 years (eg, 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 5. Known central nervous system involvement by leukemia. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3 MDS Cohort: Modified Overall Response (mOR) Rate | Approximately 24 months | The mOR will be defined as the percentage 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 timepoint (t) (AUC0-t) Of BGB-11417 When Administered Alone and 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) | — |
| Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Administered Alone and 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) | — |
| 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 Administered Alone and When Co-administered With Posaconazole | 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 | Cycle 2 | — |
| Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs | Approximately 24 months | — |
| 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) | — |
| Part 1 And 2: Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | Approximately 24 months | — |
| 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 percentage 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| 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 | — |
| Part 3: Number Of Participants Experiencing TEAEs | Approximately 24 months | — |
| Part 3: Complete Response Rate | Approximately 24 months | CR will be defined as the percentage 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: Overall Response Rate (ORR) | 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) | 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) | 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) | 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) | 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 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. |
| 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 |
| 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 |
| 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. |
| Part 3 MDS Cohort: Number of participants with Transfusion Independence | Approximately 24 months | Transfusion independence will be defined as the percentage 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 | Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose) | — |
| Part 3 MDS cohort: Partial Hematologic Recovery CRh | Approximately 24 months | Percentage of participants with partial hematologic recovery will be reported |
| Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery | Approximately 24 months | Percentage 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 | 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 | Approximately 24 months | Percentage of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR) |
| Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate | Approximately 24 months | CRi will be defined as the percentage of participants whose BOR is CRi. |
| 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) | — |
| Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh) | Approximately 24 months | — |
| Parts 1 And 2 MDS Cohort: mOR Rate | Approximately 24 months | — |
| 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 | — |
| Parts 1 And 2: Terminal Half-life (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 | — |
| 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 | — |
| 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 | — |
| Parts 1 And 2: Apparent Total Clearance Of Azacitidine From Plasma (CL/F) When Coadministered With BGB-11417 | 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 | Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose | — |
Countries
Australia, China, France, Germany, Italy, New Zealand, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTBeiGene
Outcome results
None listed