Clinical Trial to Assess the Safety and Tolerability of the Combination of Low-dose Cytarabine or Azacitidine Plus Venetoclax and Quizartinib in Newly Diagnosed AML Patients Aged Equal or More Than 60 Years Old
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Age More 60yr
- De Novo
- Leukemia Myeloid Acute
- Type
- Interventional
- Phase
- Phase 1Phase 2
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Phase 1: Study treatment will start at level 1 and therapeutic level will be escalated or descalated depending on the apparition of DLT. DLT will be monitored during cycle 1 and it is defined as any grade 3-4 related extrahematological toxicity or grade 4 neutropenia not recovered on day 56 since C1D1 not attributable to persistent leukemia. Phase I will consist of two parallel dose escalation cohorts, with consecutive assignment to each group (first patient will be assigned to AZA-based schedule, second to LDAC-based, third to AZA-based, etc). Phase II includes two treatment arm groups (AZA-based RP2D vs. LDAC-based RP2D). Patients will be enrolled at diagnosis, within a maximum 28 days screening period, will be assessed for eligibility and therefore randomized to follow the assigned treatment arm (open label design). All screening activities will be performed after patient's informed consent form is signed. Patients will start the assigned regimen 48h maximum after randomization.Masking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 60 years and 125 years
- Gender
- Both males and females
Description
The prognosis of AML in elderly patients remain very poor and without significant advances in last decades. AML is a heterogeneous disease in which many altered molecular pathways could contribute to the disease. Thus, curative approaches have been based on highly eradicating regimens using high-dos...
The prognosis of AML in elderly patients remain very poor and without significant advances in last decades. AML is a heterogeneous disease in which many altered molecular pathways could contribute to the disease. Thus, curative approaches have been based on highly eradicating regimens using high-dose chemotherapy. However, the low rate of CRs and the high rate of deaths due to toxicity and relapses in elderly patients should stimulate the development of new regimens that overcome these therapeutic obstacles. In recent years, there are a series of new drugs under development that allow the design of sequential combination therapies in this vulnerable population. These drugs have an acceptable toxicity profile and are apparently effective in monotherapy or even in combination, being able to improve the CR rate in this population. The investigators hypothesize that the combination of two targeted drugs that have different mechanisms of action could be capable of breaking the viability of leukemic cells as well as their proliferative qualities, and therefore prolong survival. In this way, the combined action of a pro-apoptotic agent (Venetoclax) and an antiproliferative agent (Quizartinib) could produce a powerful antileukemic effect, preventing the adaptive escape mechanisms of leukemic cells. The investigators have designed a phase I-II trial based on the combination of three drugs regimen LDAC or Azacitidine + Venetoclax + Quizartinib that in this population could be well tolerated by a sequential type administration. The first objective is to achieve rapid control of the disease, using two different schemes, one based in Azacitidine and the other in LDAC, by dose escalation in phase I of the trial. The second goal is to prevent relapse through a maintenance schedule. Phase II will study the efficacy and safety of the recommended dose for Phase II.
Tracking Information
- NCT #
- NCT04687761
- Collaborators
- Not Provided
- Investigators
- Principal Investigator: Pau Montesinos, MD Hospital Universitario La Fe Principal Investigator: Juan Bergua, MD Hospital San Pedro Alcántara Study Chair: Carmen López-Carrero García Fundación PETHEMA
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