Open-label Study of FT-2102 With or Without Azacitidine or Cytarabine in Patients With AML or MDS With an IDH1 Mutation

Official Title

A Phase 1/2, Multicentre, Open-label Study of FT-2102 as a Single Agent and in Combination With Azacitidine or Cytarabine in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome With an IDH1 Mutation

Summary:

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 (olutasidenib) as a single agent or in combination with azacitidine or cytarabine. The Phase 1 stage of the study is split into 2 distinct parts: a dose escalation part, which will utilize an open-label design of FT-2102 (olutasidenib) (single agent) and FT-2102 (olutasidenib) + azacitidine (combination agent) administered via one or more intermittent dosing schedules followed by a dose expansion part. The dose expansion part will enroll patients in up to 5 expansion cohorts, exploring single-agent FT-2102 (olutasidenib) activity as well as combination activity with azacitidine or cytarabine. Following the completion of the relevant Phase 1 cohorts, Phase 2 will begin enrollment. Patients will be enrolled across 8 different cohorts, examining the effect of FT-2102 (olutasidenib) (as a single agent) and FT-2102 (olutasidenib) + azacitidine (combination) on various AML/MDS disease states.

Trial Description

Primary Outcome:

• Maximum Tolerated Doses (MTDs) or Maximum Evaluated Doses (MEDs) [Phase 1]
• Number of Participants with a Dose Limiting Toxicity (DLT) [Phase 1]
• Doses recommended for future studies [Phase 1]
• Complete Response (CR and CRh) Rate of FT-2102 (olutasidenib) single-agent or in combination with Azacitidine in patients with AML/MDS [Phase 2 Cohorts 1, 3-8]
• 4-Month Relapse Free Survival (RFS) of FT-2102 (olutasidenib) single-agent [Phase 2 Cohort 2]

• Area under the plasma concentration versus time curve (AUC) [Phase 1 and Phase 2]
• Peak Plasma Concentration (Cmax) [Phase 1 and Phase 2]
• Time of peak plasma concentration Tmax [Phase 1 and Phase 2]
• Time for half of the drug to be absent in blood stream following dose (T 1/2) [Phase 1 and Phase 2]
• Rate at which drug is removed from blood stream (CL/F) [Phase 1 and Phase 2]
• Rate of drug distribution within the blood stream (Vd/F) [Phase 1 and Phase 2]
• Evidence of antileukemic or antimyelodysplastic activity of FT-2102 (olutasidenib) as determined by CR, CRh, CRi, MLFS, Marrow CR, PR, and SD as a single-agent or in combination with azacitidine or cytarabine [Phase 1]
• Incidence and severity of adverse events, clinical laboratory abnormalities, and changes in ECG parameters as assessed by CTCAE v4.0 as a single-agent or in combination with azacitidine [Phase 2]
• Additional measures of antileukemic or antimyelodysplastic activity as determined by CRi, MLFS, Marrow CR, PR, Overall Response (OR), and Stable Disease (SD) of FT-2102 (olutasidenib) alone or in combination with azacitidine [Phase 2]
• Time to Response (TTR) [Phase 2]
• Duration of Response (DOR) [Phase 2]
• Event-Free Survival (EFS) [Phase 2]
• Overall Survival (OS) [Phase 2]
• Relapse Free Survival (RFS) [Phase 2]

View this trial on ClinicalTrials.gov