NCT04687761

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

A Phase I-II, Multicentre, Open Label Clinical Trial to Assess the Safety and Tolerability of the Combination of Low-dose Cytarabine or Azacitidine, Plus Venetoclax and Quizartinib in Newly Diagnosed Acute Myeloid Leukemia Patients Aged Equal or More Than 60 Years Old Ineligible for Standard Induction Chemotherapy

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 84 (estimated)
• Sponsor: PETHEMA Foundation · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed 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-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.

Conditions

• Leukemia, Myeloid, Acute
• De Novo
• Age More 60yr

Interventions

Type	Name	Description
DRUG	Azacitidine	AZA 75 mg/m2/daily SC days 1 to 7 or on a 5-on/2-off \[weekend\]/2-on schedule in 28-day cycle
DRUG	Venetoclax	Venetoclax (ramp-up) 400 mg/daily oral days 1 to 28
DRUG	Quizartinib	Quizartinib 40 mg/daily oral, days, 8 to 28
DRUG	Cytarabine	Low-dose subcutaneous cytarabine (LDAC) 20 mg/m2/daily SC, days 1 to 10
DRUG	Venetoclax	Venetoclax (ramp-up) 600 mg/daily oral, days 1 to 28
DRUG	Quizartinib	Quizartinib 40 mg/daily oral, days 8 to 28

Timeline

• Start date: 2020-11-04
• Primary completion: 2024-11-01
• Completion: 2024-11-01
• First posted: 2020-12-29
• Last updated: 2022-09-08

Locations

15 sites across 1 country: Spain