- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03113071
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
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
1
Phase
- 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
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Philadelphia, Pennsylvania, United States, 19111
- Jeans Hospital
-
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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
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
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
- For patients with refractory disease they must be at least 4 weeks out from most recent therapeutic intervention.
- Age > 18 years.
- ECOG performance status 0 - 2.
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
- Ability to understand and willingness to sign a written informed consent and HIPAA consent document.
- 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:
- 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.
- Patients receiving any other investigational agents.
- Patients with known brain metastases, active infection, or untreated CNS leukemia.
- Patients with prior or current history of digoxin exposure.
- 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.
- Patients requiring treatment with one or more beta-blockers (metoprolol, atenolol, propranolol) or calcium channel blockers with AV-nodal blocking activity (verapamil, diltiazem).
- Patient with history of prior exposure to decitabine.
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
- 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.
- 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.
- 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 |
Intervention / Treatment |
---|---|
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.
|
Decitabine will be administered in combination with Digoxin
Decitabine will be administered in combination with Digoxin
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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.
|
Decitabine will be administered in combination with Digoxin
Decitabine will be administered in combination with Digoxin
|
What is the study measuring?
Primary Outcome Measures
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
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1-2 months
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Number of Grade II and IV Toxicities Due to of the Combination Therapy of Decitabine in Combination With Digoxin
Time Frame: 1-3 years
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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.
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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
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1-3 years
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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
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)
June 2, 2017
Primary Completion (Actual)
January 8, 2019
Study Completion (Actual)
March 11, 2019
Study Registration Dates
First Submitted
April 10, 2017
First Submitted That Met QC Criteria
April 12, 2017
First Posted (Actual)
April 13, 2017
Study Record Updates
Last Update Posted (Actual)
March 16, 2021
Last Update Submitted That Met QC Criteria
February 22, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic Syndromes
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protective Agents
- Cardiotonic Agents
- Decitabine
- Digoxin
Other Study ID 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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