IMPACT-AML: Randomized Pragmatic Clinical Trial for Relapsed or Refractory AML

Prior treatment

• Previous refractoriness or loss of response during ongoing venetoclax therapy;
• Previous alloHSCT;
• Severe cardiac pathology:
  • uncontrolled arterial hypertension;
  • stable angina III-IV functional classes;
  • unstable angina and/or myocardial infarction less than 6 months before inclusion in the study;
  • heart failure stages IIb-III, NYHA functional classes III-IV
  • uncontrolled cardiac rhythm disturbances (≥ 2 grade CTCAE 5.0) or clinically significant ECG abnormalities.
• Major surgical interventions underwent less than 14 days before inclusion in the study.

Other illness

• Failure of the subject to follow the study protocol;
• History of other malignancies within the past 3 years, excluding squamous cell and basal cell skin cancers, carcinoma in situ of the cervix, breast, or other non-invasive malignancies, which, in the opinion of the investigator, are considered adequately treated and have a minimal risk of recurrence within 3 years;

Lab values

• Chronic kidney disease with GFR ≤ 30 ml/min/1.73 m2 (according to the CKD-EPI Creatinine Equation);
• Increased liver function tests above the following values:
  • Total bilirubin \> 1,5 above the normal range;
  • AST, ALT \> 10 above the normal range.

Other

• Late relapsed AML;
• Isolated extramedullary relapse;
• MRD relapse without development of bone marrow relapse of AML;
• Acute promyelocytic leukemia;
• Pregnancy and/or lactation period;
• Refusal of patients with preserved reproductive potential to use highly effective methods of contraception during the period of participation in the study;
• Lack of signed informed consent to participate in the study;
• Participation in any other clinical trial;
• Uncontrolled infectious complications;
• ECOG ≥ 3;
• Cirrhosis classes B-C according to the Child-Pugh classification

• Age ≥ 18 years;
• Primary refractory AML;
• Early relapsed AML;
• A signed informed consent to participate in the study.