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

Sponsor
PETHEMA Foundation
Study ID
NCT04687761
Phase
PHASE1/PHASE2
Status
Completed

Conditions

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

Eligibility Criteria

Sex
ALL
Age
60 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Azacitidine — DRUG
    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
  • Venetoclax — DRUG
    Venetoclax (ramp-up) 400 mg/daily oral days 1 to 28
  • Quizartinib — DRUG
    Quizartinib 40 mg/daily oral, days, 8 to 28
  • Cytarabine — DRUG
    Low-dose subcutaneous cytarabine (LDAC) 20 mg/m2/daily SC, days 1 to 10
  • Venetoclax — DRUG
    Venetoclax (ramp-up) 600 mg/daily oral, days 1 to 28
  • Quizartinib — DRUG
    Quizartinib 40 mg/daily oral, days 8 to 28

Study Details

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

Key Dates

Start date
Nov 4, 2020
Status verified
May 2026
Primary completion
Nov 30, 2024
Completion
May 30, 2025

Study Design

Enrollment
113 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: AZA-Based
    Azacitidine 75 mg/m2/daily SC on a 5-on/2-off \[weekend\]/2-on schedule in 28-day cycle plus Venetoclax (ramp-up) 400 mg/daily oral, days 1 to 28 plus Quizartinib phase I/RP2D mg/daily oral, days 8 to 14-28. If 1 DLT is observed among these 3 patients, additional 3 subjects will receive the level 2 dose, and it will be recommended in the absence of DLT between them. If \>1 DLT occurs in these 6 level 2 patients, the dose administered in the level 1 will be the RP2D of the AZA-based schedule. AZA and Venetoclax doses will remain the same in all levels and only the dose of Quizartinib will be modificated according to the following table: Escalation-Quizartinib dose-Quizartinib duration; Level-2 -30 mg/daily-Days 8 to 14; Level-1 -30 mg/daily-Days 8 to 21; Level1-40 mg/daily Days 8 to 28; Level2-60 mg/daily-Days 8 to 28. In phase II, patients randomized to this arm, will receive the recommended phase 2 dose (RP2D) regimen of AZA + Venetoclax + Quizartinib regimen (30 patients).
  • Experimental: LDAC-Based
    Low-dose subcutaneous cytarabine 20 mg/m2/daily SC, days 1 to 10 plus Venetoclax (ramp-up) 600 mg/daily oral, days 1 to 28 plus Quizartinib phase I/RP2D mg/daily oral, days 8 to 14-28. If 1 DLT is observed among these 3 patients, additional 3 subjects will receive the level 2 dose, and it will be recommended in the absence of DLT between them. If \>1 DLT occurs in these 6 level 2 patients, the dose administered in the level 1 will be the RP2D of the LDAC-based schedule. LDAC and Venetoclax doses will remain the same in all levels and only the dose of Quizartinib will be modificated according to the following table: Escalation-Quizartinib dose-Quizartinib duration; Level-2 -30 mg/daily-Days 8 to 14; Level-1 -30 mg/daily-Days 8 to 21; Level1-40 mg/daily-Days 8 to 28; Level2-60 mg/daily-Days 8 to 28. In phase II, patients randomized to this arm, will receive the recommended phase 2 dose (RP2D) regimen of LDAC + Venetoclax + Quizartinib regimen (30 patients).

Primary Outcome Measure

Phase I: Recommended phase 2 dose (RP2D) [ Time Frame: Approximately 6 months after first patient first visit (FPFV) ]

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