Trial for Relapsed or Refractory AML Patients Combining Cytarabine and Mitoxantrone With Venetoclax (RELAX)

Exclusion Criteria

• •Acute promyelocytic leukemia (AML M3)
• •CNS involvement or subjects with extramedullary disease only
• •Known hypersensitivity to excipients of the preparation or any agent given in association with this study including cytarabine or mitoxantrone
• •Intended hematopoietic stem cell transplantation planned as early conditioning from aplasia without previous blood count recovery
• •Cumulative previous exposure to anthracyclines of \>410 mg/m2 doxorubicin equivalents
• •Acute GVHD ≥ grade 2, extensive chronic GVHD or requiring systemic immunosuppressive therapy within 2 weeks prior to start of study treatment
• •HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections).
• •Inability to swallow oral medications
• •Any malabsorption condition
• •Cardiovascular disability status of New York Heart Association (NYHA) Class ≥ 2.
• •Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• •Chronic respiratory disease that requires continuous oxygen use.
• •White blood cell count \> 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
• •AML relapse treatment with any investigational or commercial drug within 14 days before enrolment. Hydroxyurea is allowed until enrolment to control peripheral WBC counts. Toxic effects of previous investigational drug treatment have to recover to Grade \<2.
• •Substance abuse, medical, psychological, or social conditions that may interfere with the subject's cooperation with the requirements of the trial or evaluation of the study results
• •Acute non-hematologic toxicities from any prior anti-leukemia therapy or from previous investigational drugs that have not resolved to Grade \<2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Evens (CTCAE), Version 5.0
• •Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment.
• •History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (Occult or prior hepatitis B virus (HBV) infection (defined as negative hepatitis B surface antigen and positive total hepatitis B core antibody) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior but cured hepatitis B are eligible. Patients positive for hepatitis C virus antibody are eligible provided PCR is negative for HCV RNA.)
• •History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C).
• •Live-virus vaccines given within 28 days prior to the initiation of study treatment