Cirtuvivint + ASTX727 for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4/5 inhibitors, CYP3A4/5 inducers

Disqualifiers: Uncontrolled infection, Cardiac disease, CNS involvement, others

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

Compensation: Varies

Number of Visits: 1

Duration: 28 days per cycle, repeated

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727 in treating patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Cirtuvivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Giving cirtuvivint alone or in combination with ASTX727 may be safe, tolerable, and/or effective in treating patients with AML and MDS.

Research Team

Evan C Chen

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

This trial is for adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who have not responded to certain treatments, including chemotherapy and other specific drugs. It's also open to older patients unfit for intensive chemotherapy. Participants need a reasonable performance status and normal bilirubin levels, unless due to Gilbert's syndrome.

Inclusion Criteria

I can take care of myself but may not be able to do any physical work.

My total bilirubin levels are within twice the normal limit, except for conditions like Gilbert's syndrome.

I have relapsed or refractory AML or MDS and have/haven't used Venetoclax.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cirtuvivint as monotherapy or in combination with ASTX727 in 28-day cycles

28 days per cycle, repeated

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last dose, then every 3 months for 2 years, then every 6 months for up to 3 years

Regular follow-up visits

Treatment Details

Interventions

• Cirtuvivint
• Decitabine and Cedazuridine

Trial Overview The trial is testing the safety and optimal dose of Cirtuvivint alone and combined with ASTX727 in AML/MDS treatment. Cirtuvivint blocks enzymes needed by cancer cells, while ASTX727 combines two drugs that help produce healthy blood cells and kill abnormal ones.

Participant Groups

Group I: Cohort III (cirtuvivint, ASTX727) Experimental Treatment 6 Interventions

Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 and ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

Group II: Cohort II (cirtuvivint) Experimental Treatment 5 Interventions

Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

Group III: Cohort I (cirtuvivint) Experimental Treatment 5 Interventions

Patients receive cirtuvivint PO QD on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+