Prospective randomized multicenter phase III trial of decitabine and venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy - DECIDER-2 trial

Prior treatment

• Any malignancy requiring chemotherapy for which the patient received chemotherapy within 3 months prior to randomization
• Participation in any other interventional clinical trial within the last 30 days before randomization
• Known or persistent abuse of medication, drugs or alcohol
• Previous treatment with DAC, azacitidine, or other DNA-hypomethylating agents, ATRA, venetoclax and other Bcl-2 inhibitors
• Previous allogeneic stem cell transplantation or solid organ transplantation
• Previous induction chemotherapy
• Previous low-dose chemotherapy (e.g. hydroxyurea, cytosine arabinoside (Ara-C), melphalan etc.) within 4 weeks prior to the first administration of study treatment, except for cytoreduction of leukocytosis ≥ 25,000/µl with hydroxyurea or Ara-C as proscribed prescribed by the clinical trial protocol; the patient must have recovered from all clinically relevant reversible non-hematologic toxicities

Other illness

• Known allergy against soy-beans or peanuts (due to ATRA excipients)
• Known hypersensitivity to or intolerance of one of the trial drugs or its constituents (e.g. other retinoids (ATRA) or sunset yellow FCF E110)
• Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
• For fertile patients: failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.
• Known positivity for HIV, Hepatitis B or Hepatitis C
• Uncontrolled bacterial, viral or fungal infection

Lab values

• Known rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
• Severe congestive heart failure, clinically unstable cardiac disease or QTc prolongation ≥ CTCAE grade 3

Other

• Acute promyelocytic leukemia (APL, FAB M3)
• Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
• Patient without legal capacity
• Person who is in a relationship of dependence/employment with the sponsor or the investigator
• Current or planned pregnancy, nursing period
• Central nervous system (CNS) leukemia

• Age ≥ 18 years
• Previously untreated AML (WHO 2016)
• ECOG ≤ 2
• White blood cell count < 25×109/L (hydroxyurea or Ara-C are permitted to meet this criterion,
• Patients considered not to benefit from the induction therapy or whom standard induction chemotherapy is not feasible; the following criteria are accepted (example): - age ≥ 75 years - - ECOG ≥ 1 - - HCT-CI ≥ 3 - adverse genetics - - patient declines standard aggressive chemotherapy - missing social support system
• Projected life expectancy of at least 8 weeks
• Written informed consent obtained according to international guidelines and local laws
• Ability to understand the nature, significance and consequences of the trial and the trial related procedures and to comply with them