Acute Myeloid LeukemiaPhase 1/2NCT03113071
Safety and Activity of Digoxin With Decitabine in Adult AML and MDS
A Phase 1/2 study testing Decitabine and Digoxin in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Fox Chase Cancer Center at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Decitabine and Digoxin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Jun 2017to 11 Mar 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Jeans Hospital
Philadelphia, Pennsylvania, 19111
About this study
Official title: 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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- Decitabine, Digoxin
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Decitabine will be administered in combination with Digoxin
DigoxinDrug
Decitabine will be administered in combination with Digoxin
| Study group | Role | What they receive |
|---|---|---|
| Newly diagnosed AML/MDS | Experimental | 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. Receives: Drug: Decitabine; Drug: Digoxin |
| Refractory or relapsed AML/MDS | Experimental | 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. Receives: Drug: Decitabine; Drug: Digoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1-2 months
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.
Measured: 1-3 years
Number of MDS Patients With Complete Remission (CR)
Complete response will be assessed by International Working Group (IWG) criteria for MDS
Measured: 1-3 years
Number of AML Patients With Complete Remission With Incomplete Blood Count Recovery (CRi)
CRi will be assessed by IWG criteria for AML
Measured: 1-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2017
- Study start2 Jun 2017
- Primary completion8 Jan 2019
- Study completion11 Mar 2019
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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. For 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.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03113071
- Sponsor's protocol ID
- 16-1061
- Other IDs
- HM-091
- Status last verified
- Feb 2021
- First submitted
- 10 Apr 2017
- Last updated
- 16 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of the Safety and Activity of Digoxin With Decitabine in Adult AML and MDS
- ClinicalTrials.gov ID
- NCT03113071
- Acronym / sponsor ID
- 16-1061
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 2 Jun 2017 (actual)
- Primary completion
- 8 Jan 2019 (actual)
- Study completion
- 11 Mar 2019 (actual)
- First posted
- 13 Apr 2017 (actual)
- Results
- Posted 16 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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. For 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.
| Arm | Type | Receives |
|---|---|---|
| Newly diagnosed AML/MDS | Experimental | Drug: Decitabine, Drug: DigoxinFor 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. |
| Refractory or relapsed AML/MDS | Experimental | Drug: Decitabine, Drug: Digoxinor 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have a confirmed diagnosis of one of the following:
- 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:
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineDecitabine will be administered in combination with Digoxin | Drug | Newly diagnosed AML/MDS, Refractory or relapsed AML/MDS |
| DigoxinDecitabine will be administered in combination with Digoxin | Drug | Newly diagnosed AML/MDS, Refractory or relapsed AML/MDS |
Primary outcome
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
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.
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Decitabine and Digoxin in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Fox Chase Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2021.