The purpose of this study is as follows:
1. Determine whether people receiving the combination treatment of olutasidenib, venetoclax, and azacitidine have the same, more, or fewer side effects compared to the usual chemotherapy treatment that people with this condition receive. 2. Determine how well the combination treatment of olutasidenib, venetoclax, and azacitidine works compared to the usual chemotherapy treatment that people with this condition receive.
Participant is an adult male or female participant aged 18-75 years considered eligible to undergo intensive induction chemotherapy at the time of signing the informed consent form (ICF).
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Newly diagnosed AML Isocitrate dehydrogenase 1 (IDH1) R132 mutated disease as assessed locally. Note: historical results from within 30 days of informed consent will be accepted if the participant did not receive systemic treatment after collection.
Secondary AML, including prior hypomethylating agents (HMA) exposure for myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN is allowed.
Relapsed/Refractory AML.
ELN (2022) favorable risk AML, except for nucleophosmin 1 (NPM1) mutated AML, which is allowed.
Acute promyelocytic leukemia (APL).
Positive Fms related receptor tyrosine kinase 3-Internal tandem duplication (FLT3-ITD) mutation.
Single group
Olutasidenib
DrugOlutasidenib will be supplied as 150 mg capsules to be administered orally, twice per day (BID) on an empty stomach (fasting at least 1 hour before or 2 hours after a meal), starting on Cycle 1 Day 1, and will be given continuously.
Venetoclax
DrugParticipants will receive Venetoclax as a 100mg tablet to be self-administered orally with a meal and water once daily, two hours after starting Olutasidenib administration, starting on Cycle 1 Day 1. The dosing regimen of Venetoclax is as follows: * Cycle 1: Days 1 - 21 over a 28-day cycle * Cycle 1 Week 1: Ramp-up dosing schedule up to 400mg (4 x 100mg/tablet) * For participants with blast clearance: Cycle 2 and beyond: Days 1 - 14 over a 28-day cycle * For participants with persistent clearance: Cycle 2 through 4: Days 1 - 21
Azacitidine
DrugParticipants will receive Azacitidine 75 mg/m2 per day via subcutaneous (SC) injection or intravenous (IV) infusion on Days 1-7 of each cycle.
Number of Participants Experiencing Excessive Toxicity
The number of participants experiencing excessive toxicity in six (6) patient safety lead-in over the duration of study treatment will be reported. All treatment-emergent adverse events (TEAEs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Composite Complete Remission (CRc)
Composite complete remission (CRc) among participants will be reported as a percentage. CRc is includes number of participants experiencing complete remission \[CR\], complete remission with partial hematologic recovery \[CRh\] or complete remission with incomplete hematologic recovery \[CRi\] after up to 3 cycles as defined by modified 2022 European LeukemiaNet (ELN) criteria.
Number of Participants Experiencing Unacceptable Toxicity
The number of participants experiencing unacceptable toxicity in entire cohort will be reported over the duration of study treatment. All toxicity will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Number of Participants Experiencing Treatment-Emergent Adverse Events
The number of participants experiencing treatment-emergent adverse events (TEAEs) will be reported over the duration of study treatment. All toxicity will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Number of Participants Experiencing Serious Adverse Events
The number of participants experiencing serious adverse events (SAEs) will be reported over the duration of study treatment. All toxicity will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Number of Participants Experiencing Adverse events of special interest (AESIs)
The number of participants experiencing adverse events of special interest (AESIs) will be reported over the duration of study treatment. All toxicity will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Click on the lead sponsor to view all of their trials.
