Cirtuvivint + ASTX727 for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Recruiting at 6 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The goal is to determine the best dose and assess the safety and side effects of a drug called cirtuvivint, both alone and in combination with another treatment, ASTX727 (a combination of decitabine and cedazuridine). Cirtuvivint aims to inhibit cancer cell growth, while ASTX727 helps eliminate abnormal cells and supports normal blood cell production. Individuals with AML or MDS that have not responded well to previous treatments might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications before joining the trial. Specifically, you cannot take strong inhibitors or inducers of certain enzymes (like CYP3A4/5) and must stop them at least 5 days before starting the trial. If you're on venetoclax, a washout period (time without taking the medication) is required.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cirtuvivint, alone or with ASTX727, might be safe and manageable for people with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Although specific reports of serious side effects have not emerged, active study continues.

ASTX727 combines two drugs: decitabine and cedazuridine. Decitabine helps create normal blood cells and eliminate abnormal ones, while cedazuridine enhances decitabine's effectiveness by preventing its rapid breakdown in the body. This combination has already received approval for other conditions, suggesting reasonable safety.

As this study is in its early stages, the primary goal is to assess safety and determine the optimal dose. While it might be well-tolerated, ongoing trials will provide more information on its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving cirtuvivint and ASTX727 for acute myeloid leukemia (AML) and myelodysplastic syndromes because they offer a novel approach compared to the standard care options like chemotherapy and hypomethylating agents. Cirtuvivint acts by targeting specific proteins involved in the cancer cell cycle, potentially leading to more precise cancer cell elimination. The addition of ASTX727, a combination of decitabine and cedazuridine, enhances the treatment by inhibiting DNA methylation, which may boost the effectiveness of cirtuvivint. This combination aims to offer a more targeted and potentially more effective treatment with fewer side effects than traditional methods.

What evidence suggests that this trial's treatments could be effective for AML and MDS?

Research has shown that cirtuvivint might stop cancer cells from growing by blocking essential enzymes. In this trial, participants in Cohort I and Cohort II will receive cirtuvivint alone, with different dosing schedules. Early results suggest that combining cirtuvivint with ASTX727, which participants in Cohort III will receive, could be effective. ASTX727 combines two drugs: decitabine and cedazuridine. Decitabine helps the bone marrow produce healthy blood cells and eliminates harmful ones, while cedazuridine prevents decitabine from breaking down too quickly in the body. This combination could enhance the treatment's power, potentially improving its effectiveness against acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). ^{1 2 6 7 8}

Who Is on the Research Team?

Evan C Chen

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06484062

NCT06484062 | Testing the Anti-cancer Drug, Cirtuvivint ... 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 ...

2. trialx.com trialx.com/clinical-trials/listings/293806/testing-the-anti-cancer-drug-cirtuvivint-and-its-combination-with-astx727-to-improve-outcomes-in-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndromes/?&radius=10&place=All%20Participating%20Sites&user_country=Germany

Testing the Anti-cancer Drug, Cirtuvivint, and ... This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727 in treating ...

3. finance.yahoo.com finance.yahoo.com/news/biosplice-therapeutics-announces-first-patient-100000897.html

Biosplice Therapeutics Announces First Patient Dosed in ... The trial (NCT06484062) is evaluating the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cirtuvivint, both as a ...

4. biospace.com biospace.com/press-releases/biosplice-therapeutics-announces-initiation-of-acute-myeloid-leukemia-aml-and-myelodysplastic-syndromes-mds-trial-sponsored-by-the-national-cancer-institute-nci

Biosplice Therapeutics Announces Initiation of Acute ... Biosplice expands its clinical candidate, cirtuvivint, as standalone treatment and combination therapy in patients with AML and MDS.

5. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/biosplice-doses-first-patient-in-aml-mds-clinical-trial/

Biosplice Doses First Patient in AML/MDS Clinical Trial Biosplice has initiated dosing in an NCI-sponsored Phase 1 study of cirtuvivint in relapsed/refractory AML and MDS, testing the selective ...

6. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-8-2024-691d9

Cirtuvivint + ASTX727 for Acute Myeloid Leukemia and ... 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 ...

7. mdsf.sparkcures.com mdsf.sparkcures.com/trial/2036/NCT06484062

Cirtuvivint - Myelodysplastic Syndrome Clinical Trials Giving cirtuvivint alone or in combination with ASTX727 may be safe, tolerable, and/or effective in treating patients with AML and MDS. Trial status. Accepting ...

8. clinicaltrials.eu clinicaltrials.eu/inn/cirtuvivint/

Cirtuvivint: A New Investigational Drug for Cancer Treatment Based on the clinical trials data, Cirtuvivint is currently being tested for several types of cancer, including: soft tissue sarcomas, small cell lung cancer, ...