Relapsed or Refractory Hematologic Malignancies Clinical Trial
Official title:
VEN-OM: Phase IB/II Study Of Safety And Efficacy Of Venetoclax When Combined With Escalating Doses Of Omacetaxine In Patients With AML Failing Treatment With Venetoclax-Containing Regimens
This will be a single arm, open label Phase Ib dose-escalation study of the combination of VEN and OM, conducted using an innovative Bayesian Optimal Interval-design, to find the MTD in participants with AML failing treatment with venetoclax-containing regimens. Treatment plan will consist of an induction phase, followed by a consolidation phase if applicable.
This is a Phase Ib study of VEN and OM, the investigator will conduct a Bayesian Optimal Interval-designed trial following the approach of Yuan et al 40 to find the MTD with a target DLT rate of 2%, 4 pre-specified doses, and between 24 and up to 30 participants. Beginning with the first participant treated at the lowest dose of OM 0.625 mg/m2 q12h with VEN 400 mg, dose escalation and de-escalation of OM will involve a comparison of the observed DLT rate (p) at the current dose with a pair of fixed, pre-specified boundary rates: λe (escalation) with p ≤ 0.157; λd (de-escalation) with p ≥ 0.238; or otherwise remain at the same dose per the dosing schedule. The trial will start with a cohort size of 1 participant (unless DLT is experienced) and escalated for each subsequent participant until the first DLT occurs and the current dose cohort is expanded to 3.40 In a simulation of these conditions with a target DLT rate of 20% (1), the percentage correct selection of the MTD is between 60% with enrollment of 20 participants and 70% with enrollment of 24 participants. Implementation of the trial design will be performed using R package 'BOIN'. If the investigator observes an unexpected toxicity in Cohort 1 the investigator will use OM 0.5 mg/m2 daily with VEN for Cohort -1 Following each cycle, participants will be evaluated for complete response (CR) by International Working Group (IWG) criteria 41 The subject visit schedule and procedures are below: Screening Visit: Physical Exam (vital signs, medical history, prior therapies, height and weight) Urine Pregnancy Test, EKG, Blood Work (Complete blood count, (CBC), basic metabolic panel (BMP), Uric Acid, Albumin, ALT/AST, bilirubin, alkaline phosphatase, protein, LDH, PT/INR, PTT and fibrinogen, HIV, Hepatitis B/C) Bone Marrow Aspirate Treatment Visits: Day 1 of Each Cycle: Physical Exam Urine Pregnancy Test, EKG, (only after 1st, 7th and 11th dose of study medication) Blood Work (Complete blood count, (CBC), basic metabolic panel (BMP), Uric Acid, Albumin, ALT/AST, bilirubin, alkaline phosphatase, protein, LDH, PT/INR, PTT and fibrinogen, HIV, Hepatitis B/C) Study Drug (s) Given Day 28 of each Cycle: Bone Marrow Biopsy Safety Follow Up Visit: (14 days + 7 days after the last dose of treatment) performed 14 days (±7 days) after the last dose of treatment. Physical Exam, Blood Work (Complete blood count, (CBC), basic metabolic panel (BMP), Uric Acid, Albumin, ALT/AST, bilirubin, alkaline phosphatase, protein, LDH, PT/INR, PTT and fibrinogen, HIV, Hepatitis B/C) Long Term Follow Up Visit: (every 2 months ±14 days for 12 months), Physical Exam Blood Work (Complete blood count, (CBC), basic metabolic panel (BMP), Uric Acid, Albumin, ALT/AST, bilirubin, alkaline phosphatase, protein, LDH, PT/INR, PTT and fibrinogen, HIV, Hepatitis B/C) ;
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| Recruiting |
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