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

February 22, 2021 updated by: Fox Chase Cancer Center

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19111
        • Jeans Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Decitabine
Decitabine will be administered in combination with Digoxin
Drug: Digoxin
Decitabine will be administered in combination with Digoxin
Experimental: 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.
Drug: Decitabine
Decitabine will be administered in combination with Digoxin
Drug: Digoxin
Decitabine will be administered in combination with Digoxin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: 1-2 months
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
Number of Grade II and IV Toxicities Due to of the Combination Therapy of Decitabine in Combination With Digoxin
Time Frame: 1-3 years
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
Number of MDS Patients With Complete Remission (CR)
Time Frame: 1-3 years
Complete response will be assessed by International Working Group (IWG) criteria for MDS
1-3 years
Number of AML Patients With Complete Remission With Incomplete Blood Count Recovery (CRi)
Time Frame: 1-3 years
CRi will be assessed by IWG criteria for AML
1-3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fox Chase Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 2, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 8, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 11, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 10, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16-1061
  • HM-091 (Other Identifier: Fox Chase Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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