Clinical trial NCT03113071 (phase 1/phase 2, status: terminated)
Conditions: acute myeloid leukemia, myelodysplastic syndromes
ICD codes: C92.A1, C92.A2, C92.61, C92.62, C92.A0, C92.60, D46.9, D46.C, D46.Z
Drugs: decitabine, digoxin
SMILES: CN(C)\N=N\C1=C(N=CN1)C(N)=O, OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1
Reason stopped: 
    slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

          1. Patients must have a confirmed diagnosis of one of the following:

               -  Newly diagnosed AML (excluding APL)

               -  Newly diagnosed intermediate-2 (INT-2) or high-risk MDS

               -  Relapsed or Refractory AML, or INT-2 or high-risk MDS

          2. For patients with refractory disease they must be at least 4 weeks out from most
             recent therapeutic intervention.

          3. Age > 18 years.

          4. ECOG performance status 0 - 2.

          5. Patients must have normal organ function as defined below:

               -  Total bilirubin within normal institutional limits

               -  AST/ALT (SGOT/SGPT) < 2 times institutional normal limits

               -  Creatinine within normal institutional limits OR

               -  Creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels
                  above institutional normal

          6. Ability to understand and willingness to sign a written informed consent and HIPAA
             consent document.

          7. Agreement on the part of any male participant to use effective contraception during
             sexual activity throughout the duration of treatment and for 2 months after
             discontinuation, for protection against the risk of embryofetal toxicity.

        Exclusion Criteria:

          1. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events (less than or equal to
             Grade 1 toxicity) due to agents administered more than 4 weeks earlier.

          2. Patients receiving any other investigational agents.

          3. Patients with known brain metastases, active infection, or untreated CNS leukemia.

          4. Patients with prior or current history of digoxin exposure.

          5. Patients requiring treatment with one or more medications known to interact adversely
             with digoxin, namely thiazide and/or loop diuretics, quinidine, ritonavir, amiodarone,
             cyclosporine, itraconazole, propafenone, spironolactone, verapamil.

          6. Patients requiring treatment with one or more beta-blockers (metoprolol, atenolol,
             propranolol) or calcium channel blockers with AV-nodal blocking activity (verapamil,
             diltiazem).

          7. Patient with history of prior exposure to decitabine.

          8. Patients eligible for intensive induction chemotherapy and "Medically unfit" based on
             a TRM score ≥ 13.1*

               -  TRM Score= A scoring model which predicts early death following intensive
                  induction chemotherapy in newly diagnosed AML.

                    -  Model looks at ECOG PS, Age, Platelet Count, Albumin, 2nd AML, WBC, %
                       Peripheral Blasts, Creatinine

                    -  Score above 13.1 associated with 31%+ chance of death after induction

          9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

         10. Known HIV-positive patients on combination anti-retroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with digoxin. In addition,
             these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy.

         11. Pregnant or breast feeding