INCLUSION CRITERIA:

          1. Patient has provided an informed consent prior to initiation of any study specific
             activities/procedures

          2. Males and females age ≥ 50 years must have histologically documented AML that is
             relapsed from, or refractory to, prior standard therapies

          3. Refractory is defined as failure to achieve CR or CRi following:

               1. At least one cycle of any anthracycline, cytarabine or fludarabine containing
                  induction regimen or persistence of disease on a nadir marrow following at least
                  one cycle of any anthracycline, cytarabine or fludarabine containing induction
                  regimen

               2. Persistent disease after at least 2 cycles of a hypomethylating agent
                  (azacytidine or decitabine) with or without venetoclax

          4. Relapse is defined as development of recurrent AML (as described by Döhner et al,
             2017)6 after CR or CRi has been achieved with a prior chemotherapy or after disease
             progression on a hypomethylating agent with or without venetoclax

          5. ECOG PS 0-2

          6. Expected survival greater than 3 months

          7. Women of child-bearing potential (i.e. women who are pre-menopausal or < 2 years post
             menopausal or not surgically sterile) must practice a highly effective method of birth
             control consistent with local regulations regarding the use of birth control methods.
             Examples: use of oral, injected or implanted hormonal methods of contraception;
             placement of an intra uterine device (IUD) or intrauterine system (IUS); male partner
             sterilization (the vasectomized partner should be the sole partner for that subject);
             true abstinence during and for 6 months after the last administered dose of CHAM or
             HAM therapy and control sub-groups (MEC and FLAG), and must have a negative serum
             pregnancy test within 1 week prior to treatment initiation and at 1st day of each
             cycle and at the end of systemic exposure. (Note: pregnant patients are excluded
             because the effects of CPI-613® (devimistat) on a fetus are unknown)

          8. Fertile men who are sexually active with a woman of childbearing potential and has not
             had a vasectomy must agree to use a barrier method of birth control eg, either condom
             with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap
             (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
             during the study period and up to 6 months after completion of the study screening,
             unless documentation of infertility exists

          9. Good state of mental health, ability to understand and willingness to sign the
             informed consent form (ICF)

         10. No radiotherapy, treatment with cytotoxic chemotherapy, treatment with biologic agents
             or any anti-cancer therapy for R/R AML within the 1 week prior to treatment with
             CPI-613® (devimistat). Hydroxyurea and/or venetoclax and oral tyrosine kinase (FLT3)
             or Isocitrate Dehydrogenase 1 and 2 (IDH1/2), BCL-2 or hedgehog inhibitors being used
             with Grade ≤ 2 toxicity can be taken until the day prior to starting of CHAM or HAM
             therapy or control sub-groups (MEC and FLAG). Previous exposure to a hypomethylating
             agent either alone or in combination with Isocitrate Dehydrogenase 1 and 2 (IDH1/2),
             BCL-2 or hedgehog inhibitors are allowed until the day prior to starting of CHAM or
             HAM therapy and control sub-groups (MEC and FLAG). Patients must have fully recovered
             from the acute, non-hematological, non-infectious toxicities of any prior treatment
             with cytotoxic drugs, radiotherapy or other anti-cancer modalities with the exception
             of alopecia (returned to baseline status as noted before most recent treatment).
             Patients with persisting, non-hematologic, non-infectious toxicities from prior
             treatment Grade ≤ 2 are eligible but must be documented as such

         11. Laboratory values ≤ 2 weeks before dosing must be:

               -  Adequate hepatic function (aspartate aminotransferase/serum glutamic-oxaloacetic
                  transaminase [AST/SGOT] ≤ 5 x upper limit of normal [ULN], alanine
                  aminotransferase/serum glutamic oxaloacetic transaminase [ALT/SGPT] ≤ 5 × ULN,
                  bilirubin ≤ 1.5 × ULN)

               -  Adequate renal function (serum creatinine clearance ≥ 60 mL/min per CockCroft
                  Gault formula)

               -  Adequate coagulation (International Normalized Ratio [INR] must be < 1.7 unless
                  on vitamin k antagonist anticoagulation)

         12. Left Ventricular Ejection Fraction (LVEF) by Transthoracic Echocardiogram (TTE) or
             Multigated Acquisition Scan (MUGA) or cardiac Magnetic Resonance Imaging (MRI),
             sufficient to safely administer mitoxantrone. Subjects must have an LVEF ≥ 45%

         13. No marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc
             interval > 480 ms for both male and female patients)

         14. No history of additional risk factors for torsade de pointes (e.g. clinically
             significant heart failure, hypokalemia, immediate family history of Long QT Syndrome)

         15. Allow only patients who experienced relapse after 1 year from previous HiDAC treatment
             or who didn't receive HiDAC previously (Note: This inclusion applies only to South
             Korea)

        EXCLUSION CRITERIA:

          1. Patients who have received cytotoxic chemotherapy treatment for their current relapsed
             or refractory AML. (Treatment with hypomethylating agents (decitabine or azacytidine)
             either alone or in combination with venetoclax are allowed until the day prior to
             starting of CHAM or HAM therapy and control sub-groups (MEC and FLAG). Targeted
             therapies including FLT3 or IDH1/2 inhibitors and/or Hydrea and/or venetoclax are
             allowed. Targeted therapies and Hydrea may be taken until the day prior to starting
             CHAM or HAM therapy or control sub-groups (MEC and FLAG)

          2. Vulnerable adult and patient whose health conditions does not allow them to give their
             consent

          3. History or evidence of any other clinically significant disorder, condition or disease
             (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic
             myocardial infection, uncontrolled cardiac arrhythmia, pericardial disease or heart
             failure New York Heart Association Class III or IV), or severe debilitating pulmonary
             disease, that would potentially increase patients' risk for toxicity and in the
             opinion of the Investigator, would pose a risk to patient safety or interfere with the
             study evaluation, procedures or completion

          4. Patients with active Central Nervous System (CNS) involvement (leukemic infiltration,
             blast in the spinal fluid)

          5. Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g.
             active peptic ulcer disease)

          6. Female patients who are pregnant or breastfeeding or planning to become pregnant or
             breastfeed during treatment and for an additional 6 months after the last dose of CHAM
             or HAM therapy or control sub-groups, MEC and FLAG (the teratogenic potential of
             CPI-613® (devimistat) is unknown). Female patients of childbearing potential with a
             positive pregnancy test assessed by a serum pregnancy test at Screening

          7. Women of childbearing potential (i.e. women who are pre-menopausal or < 2 years
             postmenopausal or not surgically sterile) unwilling to practice a highly effective
             method of birth control consistent with local regulations regarding the use of birth
             control methods during treatment and for 6 months after completion of CHAM or HAM
             therapy or control sub-groups, MEC and FLAG for AML

          8. Male patients with a pregnant partner who are unwilling to practice abstinence or use
             a condom during treatment and for 6 months after completion of CHAM or HAM therapy or
             control sub-groups, MEC and FLAG

          9. Male patients unwilling to abstain from donating sperm during treatment and for 6
             months after completion of CHAM or HAM therapy or control sub-groups, MEC and FLAG
             with potential highest teratogenic risk

         10. Known hypersensitivity to study treatment drugs or any of the excipient(s) contained
             in the drug formulation

         11. Life expectancy less than 3 months

         12. Any condition or abnormality which may, in the opinion of the investigator, compromise
             the safety of patients

         13. Unwilling or unable to follow protocol requirements

         14. Patients with large and recurrent pleural or peritoneal effusions requiring frequent
             drainage (e.g. weekly)

         15. Patients with any amount of clinically significant pericardial effusion that requires
             drainage.

         16. Evidence of ongoing, uncontrolled bacterial, viral or fungal infection

         17. Patients with known human immunodeficiency virus infection

         18. History of other malignancy within the past 5 years, with the following exception(s):

               1. Malignancy treated with curative intent and with no known active disease present
                  for ≥ 5 years before enrolment and felt to be at low risk for recurrence by the
                  treating physician

               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of recurrent or residual disease

               3. Adequately treated cervical carcinoma in situ without evidence of disease

               4. Prostate cancer Stage 1

         19. Patients receiving any other standard or investigational treatment for AML, or any
             other investigational agent for any indication within the past 1 week prior to
             initiation of CPI-613® (devimistat) treatment (the use of Hydrea and/or venetoclax,
             oral tyrosine kinase inhibitors FLT3 or IDH 1/2 inhibitors are allowed until the day
             prior to starting CHAM or HAM therapy or control sub-groups, MEC and FLAG. Previous
             exposure to a hypomethylating agent either alone or in combination with venetoclax are
             allowed until the day prior to starting of CHAM or HAM therapy and control sub-groups
             (MEC and FLAG))

         20. Patients who have received immunotherapy of any type within the past 1 week prior to
             initiation of CPI-613® (devimistat) treatment

         21. Requirement for immediate palliative treatment of any kind including minor surgery

         22. Patients who have received a chemotherapy regimen with autologous stem cell support
             (bone marrow transplantation) within 6 months of starting CHAM or HAM therapy or
             control sub-groups (MEC and FLAG)

         23. Patients who have had allogenic bone marrow transplantation within the last 6 months.
             Patients who have had an allogenic transplant more than 6 months ago are eligible
             provided they have no graft vs host disease. (Note: Exclude only patients with active
             GVHD requiring therapy with immunosuppressive agents and not patients with stable GVHD
             not requiring immunosuppression.)

         24. Cytarabine contraindications

               -  Hypersensitivity to the cytarabine or to any of the excipients of cytarabine
                  injection

               -  Anemia, leucopenia and thrombocytopenia of non-malignant aetiology (e.g bone
                  marrow aplasia); unless the clinician feels that such management offers the most
                  hopeful alternative for the patient

               -  Degenerative and toxic encephalopathies, especially after the use of methotrexate
                  or treatment with ionizing radiation

         25. Mitoxantrone contraindications

               -  Mitoxantrone Sterile Concentrate is contraindicated in patients who have
                  demonstrated prior hypersensitivity to mitoxantrone hydrochloride, other
                  anthracyclines or any of its components. Use in patients with profound bone
                  marrow suppression is a relative contraindication depending on the clinical
                  circumstances

               -  Mitoxantrone Sterile Concentrate should not be used during pregnancy or lactation

         26. Strong CYP450 inducers should be prohibited

         27. Etoposide contraindications

             •. Contraindicated in patients with a history of a severe hypersensitivity reaction to
             etoposide products

         28. Fludarabine contraindications

             •. Contraindicated in those patients who are hypersensitive to this drug or its
             components

         29. Filgrastim contraindications •. Contraindicated in patients with known
             hypersensitivity to E coli-derived proteins, Filgrastim, or any component of the
             product