Entinostat + Pembrolizumab for Myelodysplastic Syndrome

Recruiting at 19 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: DNMTi

Must not be taking: Anti-PD-1, HDACi

Disqualifiers: Active cancers, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 12 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial studies the side effects and best dose of entinostat when given together with pembrolizumab in treating patients with myelodysplastic syndrome after deoxyribonucleic acid (DNA) methyltransferase inhibitor (DNMTi) therapy failure. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving entinostat together with pembrolizumab may work better in treating patients with myelodysplastic syndrome after DNMTi therapy failure.

Research Team

Amer M. Zeidan

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

This trial is for adults with Myelodysplastic Syndrome or Preleukemia who haven't improved after treatment with hypomethylating agents. They should have proper kidney and liver function, no severe illnesses, and not be pregnant or breastfeeding. HIV-positive patients can join if they meet certain health criteria.

Inclusion Criteria

I am HIV positive, on effective treatment, with an undetectable viral load and a CD4 count over 250.

My MDS or AML treatment with DNMTi didn't work or my cancer progressed after it.

My kidney function, measured by creatinine clearance, is normal or above.

Exclusion Criteria

I have hepatitis B or C, but my viral load is undetectable, with or without treatment.

I have an autoimmune disease but my thyroid condition is stable with treatment.

I am allergic to pembrolizumab or similar medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive entinostat orally and pembrolizumab intravenously in a dose-escalation study. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

4 visits (in-person)

Extended Treatment

Participants who achieve an objective response or maintain stable disease may continue treatment for up to 1 year.

1 year

Follow-up

Participants are monitored monthly for safety and effectiveness after treatment completion.

6 months

6 visits (in-person)

Treatment Details

Interventions

• Entinostat
• Pembrolizumab

Trial Overview The trial tests the combination of Pembrolizumab (an immune system booster) and Entinostat (a growth blocker for cancer cells) in patients whose previous DNA methyltransferase inhibitor therapy didn't work. It aims to find the safest dose and see how well these drugs work together.

Participant Groups

Group I: Treatment (entinostat, pembrolizumab) Experimental Treatment 2 Interventions

Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year.

Entinostat is already approved in China, European Union for the following indications:

Approved in China as Entinostat for:

• Cancer

Approved in European Union as Entinostat for:

• Orphan Drug designation for cancer treatment

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+