Safety and Activity of Digoxin With Decitabine in Adult AML and MDS

NCT ID: NCT03113071

Last Updated: 2021-03-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-02
• Study Completion Date: 2019-03-11

Brief Summary

The primary hypothesis is that digoxin can be safely added to decitabine and will increase the response rates in medically unfit patients with newly diagnosed AML/MDS or those with relapsed/refractory AML/MDS. Furthermore, it is hypothesized that the addition of digoxin to decitabine will result in distinct epigenetic alterations in AML/MDS patients.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Newly diagnosed AML/MDS

For Group#1 a total of 37 patients with newly diagnosed MDL or MDS will be enrolled, including the eligible patients originally enrolled in the phase Ib portion (safe dose group) of the study, with the goal of determining the clinical activity of our experimental regimen. In the phase II segment, all new patients who are enrolled will initially be randomized in a 1 to 1 fashion to receive decitabine alone or decitabine plus digoxin for one cycle before receiving decitabine plus digoxin for all subsequent cycles for a total of 6 cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Decitabine will be administered in combination with Digoxin

Digoxin

Intervention Type: DRUG

Decitabine will be administered in combination with Digoxin

Refractory or relapsed AML/MDS

or Group#2 the target will be to enroll a total of 60 patients with relapsed or refractory AML/MDS, including the eligible patients enrolled in the phase Ib group. This group will have randomization and treatments similar to Group#1.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Decitabine will be administered in combination with Digoxin

Digoxin

Intervention Type: DRUG

Decitabine will be administered in combination with Digoxin

Interventions

Decitabine

Decitabine will be administered in combination with Digoxin

Intervention Type: DRUG

Digoxin

Decitabine will be administered in combination with Digoxin

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fox Chase Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Jeans Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HM-091

Identifier Type: OTHER

Identifier Source: secondary_id

16-1061

Identifier Type: -

Identifier Source: org_study_id