Inqovi for Clonal Cytopenia

Overseen By Maximilian Stahl, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Lachelle D. Weeks, MD, PhD

Must not be taking: Cytotoxic chemotherapy, Immunomodulatory agents

Disqualifiers: Concurrent malignancy, Inherited bone marrow disorder, MDS, others

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

Compensation: Varies

Number of Visits: 21

Duration: 12 months

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential risks and benefits of an oral drug called Inqovi, a combination of decitabine and cedazuridine, for individuals with high-risk Clonal Cytopenia of Unknown Significance (CCUS). Some participants will receive the drug, while others will undergo close observation to compare outcomes. The trial seeks participants with unexplained low blood cell counts for at least four months and a specific genetic change identified in blood tests. As an Early Phase 1 trial, this research aims to understand the treatment's effects in people, offering participants an opportunity to contribute to groundbreaking medical research.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on anti-cancer therapies or have a concurrent primary malignancy requiring treatment, you may not be eligible. It's best to discuss your specific medications with the trial team.

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

Research has shown that oral treatment with decitabine/cedazuridine (Inqovi) has a safety profile similar to the intravenous form, decitabine. People taking the oral tablets might experience similar side effects. A common side effect is low blood cell counts, which can be serious and lead to complications. One study found a slightly higher chance of these low blood counts during the first treatment cycle with the oral tablets compared to the intravenous version.

Data from previous studies indicate that about 6% of participants experienced severe side effects, similar to those seen with the intravenous form. Despite these potential risks, the treatment has generally been well-tolerated. This information can help prospective participants understand the treatment's safety when considering joining the clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Inqovi for treating clonal cytopenia because it combines two active ingredients, decitabine and cedazuridine, into an oral formulation. This is significant because traditional treatments often rely on intravenous administration, which can be more cumbersome for patients. Decitabine works by inhibiting DNA methylation, potentially reactivating tumor suppressor genes, while cedazuridine boosts decitabine's effectiveness by preventing its breakdown. This combination could offer a more convenient and potentially more effective treatment option for patients with clonal cytopenia.

What evidence suggests that Decitabine/cedazuridine might be an effective treatment for Clonal Cytopenia?

In this trial, participants in the Inqovi Cohort will receive a combination of decitabine and cedazuridine, known as Inqovi. Studies have shown that Inqovi can effectively treat blood disorders similar to clonal cytopenia. Previous research indicated that this treatment helped 62% of patients, with many experiencing a positive change in their condition. Specifically, the treatment led to an average survival time of about 31.7 months for patients with conditions like myelodysplastic syndromes, which resemble clonal cytopenia. While these results are promising, common side effects include low blood cell counts, potentially causing infections or tiredness. Overall, these findings suggest Inqovi might improve outcomes in clonal cytopenia, but more research is needed to fully understand its potential for this specific condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Lachelle Weeks, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with high-risk Clonal Cytopenia of Unknown Significance (CCUS), which includes conditions like low blood cell counts, anemia, and thrombocytopenia. Participants should not have other health issues that could interfere with the study.

Inclusion Criteria

I will use effective birth control during and up to 6 months after treatment.

Unexplained cytopenia(s) for at least 4 months (Hemoglobin (Hgb) <12 g/dL for women, <13g/dL for men; Absolute neutrophil count (ANC) < 1.8 × 10^9/L; Platelet count (Plt) <150 × 10^9/L)

I have a Duffy-null genotype with low blood count or low platelets.

Exclusion Criteria

I have a genetic condition that affects my bone marrow or increases my risk of blood cancer.

Laboratory evidence indicative of clinically significant red cell hemolysis

I have a precursor condition to blood cancer.

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 oral Decitabine/cedazuridine for 12 cycles, each cycle lasting 28 days

12 months

In-clinic visits on Cycle 1 days 8, 15, 22 and Cycle 2-12 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

In-clinic visits at Cycle 19 Day 21, Cycle 25 Day 1, Cycle 31 Day 1, and Cycle 36 Day 28

Observation

Participants in the observational cohort undergo regular assessments without active treatment

36 months

In-clinic visits with assessments at specified cycles

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine/cedazuridine

Trial Overview The trial is testing the effects of early treatment using Decitabine/cedazuridine (DEC/CED), an oral medication, compared to just observing patients without active treatment. DEC/CED inhibits certain cellular processes that may be involved in CCUS.

How Is the Trial Designed?

Group I: Inqovi Cohort Experimental Treatment 1 Intervention

Participants will be enrolled and will complete: * Baseline visit. * In-clinic visits with assessments: Cycle 1 days 8, 15, and 22. * In-clinic visits with assessments and bone marrow biopsies: Cycles 2 - 12 Day 1. * Cycle 1 - 12: • Days 1 - 5 of 28 day cycle: Predetermined dose of Inqovi 1x daily. * End of Treatment visit, Cycle 13 Day 1, with assessments and bone marrow biopsy. * Follow up in-clinic visits with assessments: Cycle 19 Day 21, Cycle 25 Day 1, Cycle 31 Day 1, and Cycle 36 Day 28. Bone marrow biopsy at Cycle 25 Day 1. * End of Study visit, Cycle 36 Day 28, with assessments and bone marrow biopsy.

Group II: Observational Cohort Active Control 1 Intervention

Participants will complete: * Baseline visit. * In-clinic visits with assessments: Cycle 7 Day 1, Cycle 13 Day, Cycle 19 Day, Cycle 25 Day 1, and Cycle 31 Day 1. * Bone marrow biopsies every 12 months at Cycle 13 Day 1 and Cycle 25 Day. * End of study visit, Cycle 36 Day 28, with assessments and bone marrow biopsy.

Who Is Running the Clinical Trial?

Lachelle D. Weeks, MD, PhD

Lead Sponsor

Trials

1

Recruited

110+

Maximilian Stahl, MD

Lead Sponsor

Trials

2

Recruited

130+

Astex Pharmaceuticals, Inc.

Industry Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Break Through Cancer

Collaborator

Trials

2

Recruited

120+

Citations

1. inqovi.com inqovi.com/hcp/efficacy-and-safety

Efficacy & Safety | INQOVI® (decitabine and cedazuridine) ... Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile ...

2. taihooncology.com taihooncology.com/us/news/2021-09-23_astex_press_release_astx727_mos_data_presented_at_mds_international_symposium/

Astex Pharmaceuticals Presents Overall Survival Data ... Study achieved median overall survival of 31.7 months; Updated efficacy data demonstrated an overall response rate of 62%, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8330281/

Clinical Efficacy and Safety of Oral Decitabine/Cedazuridine in ... Most common Treatment-Emergent AEs of Grade ≥3 regardless of causality were neutropenia in 51.5%, thrombocytopenia in 50%, anemia in 40%, ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2025.2577861?src=

Real-world experience and outcomes of decitabine ... Real-world experience and outcomes of decitabine/cedazuridine or azacitidine for the treatment of myelodysplastic syndrome/chronic ...

5. onclive.com onclive.com/view/prolonged-overall-survival-observed-with-oral-decitabine-cedazuridine-in-mds-and-cmml

Prolonged Overall Survival Observed With Oral Decitabine ... The oral, fixed-duration combination of decitabine and cedazuridine induced a median overall survival of 31.7 months in patients with intermediate- and high- ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/212576Orig1s000RiskR.pdf

212576Orig1s000 - accessdata.fda.gov 9 For Inqovi studies, the 6% deaths within 30 days of pooled safety data set is consistent with data from IV decitabine. The medical officer.

7. inqovi.com inqovi.com/side-effects

INQOVI® (decitabine and cedazuridine) tablets Side Effects INQOVI may cause serious side effects, such as low blood cell counts. Low blood counts are common with INQOVI but can also be serious and can lead to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06802146

NCT06802146 | Early Intervention in High Risk CCUS This is an open-label, multicenter pilot study testing the feasibility and safety of early pharmacologic intervention, decitabine/cedazuridine, in participants ...

9. cda-amc.ca cda-amc.ca/sites/default/files/pcodr/Reviews2021/10228Decitabine-CedazuridineMDS_fnCGR_REDACT_Post22Sep2021_final.pdf

Clinical Report Data on the safety profile of decitabine/cedaruzidine was assessed in the ASCERTAIN and ASTX727 trial. Decitabine and cedazuridine was overall quite well ...