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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase Ib/II Study of the Safety and Activity of Digoxin With Decitabine in Adult AML and MDS

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03113071
• Other study ID #: 16-1061
• Secondary ID: HM-091
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 2, 2017
• Est. completion date: March 11, 2019

Study information

• Verified date: February 2021
• Source: Fox Chase Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 11, 2019
• Est. primary completion date: January 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Intervention

Drug:
• Decitabine
Decitabine will be administered in combination with Digoxin
• Digoxin
Decitabine will be administered in combination with Digoxin

Locations

Country	Name	City	State
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Jeans Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Fox Chase Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of Digoxin in Combination With Standard Dose of Decitabine in Patients Newly Diagnosed AML/MDS or Those With Relapsed or Refractory AML/MDS Considered Unfit for Induction Therapy	Maximum tolerated dose of digoxin in combination with standard dose of decitabine will be determined by a standard 3+3 dose de-escalation design	1-2 months
Primary	Number of Grade II and IV Toxicities Due to of the Combination Therapy of Decitabine in Combination With Digoxin	The safety of the combination therapy will be determined by the number of grade III or IV non-hematologic toxicities as per NCI CTCAE v4.03 criteria.	1-3 years
Primary	Number of MDS Patients With Complete Remission (CR)	Complete response will be assessed by International Working Group (IWG) criteria for MDS	1-3 years
Primary	Number of AML Patients With Complete Remission With Incomplete Blood Count Recovery (CRi)	CRi will be assessed by IWG criteria for AML	1-3 years