This is a multi-center, open-label, non-randomized, two-part Phase I/Ib study of RP7214 in combination with azacitidine in patients with AML, MDS and CMML. Part I is a 3+3 dose-escalation study to identify the MTD/RP2D of RP7214 and azacitidine combination in patients with AML, MDS, and CMML. Part II is a dose-expansion study to evaluate the clinical activity and safety of RP7214 and azacitidine combination in AML.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
RP7214 will be administered daily twice a day orally; Azacitidine will be administered from Days 1 to 7 of each 28-day cycle
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of RP7214 in combination with azacitidine
The maximum tolerated dose will be defined as the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels.
Time frame: 28 days
Tmax
Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP7214
Time frame: 35 days
Objective Response Rate (ORR)
Defined as the percentage of patients who achieve Complete Remission (CR), Complete Remission with incomplete bone marrow recovery (CRi) and Partial Remission (PR)
Time frame: 2 years
Clinical Benefit Rate (CBR)
Defined as the percentage of patients achieving a CR, CRi, PR and Stable Disease (SD) lasting for at least 8 weeks.
Time frame: 2 years
Duration of Remission
Defined as the number of days from the date of first remission (CR, CRi, or PR) to the recurrence or Progressive Disease (PD)
Time frame: 2 years
Percentage of patients requiring blood and/or platelet transfusions
Defined as number of patients requiring blood and/or platelet transfusions
Time frame: 2 years
Cmax
Pharmacokinetics: Maximum Concentration (Cmax) of RP7214
Time frame: 35 days
AUC
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Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP7214
Time frame: 35 days