Oral Decitabine + Cedazuridine for Myelodysplastic Syndrome

Recruiting at 18 trial locations

Overseen By Taiho Oncology, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Taiho Oncology, Inc.

Must not be taking: Azacitidine, Decitabine, Lenalidomide, others

Disqualifiers: Uncontrolled infections, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an oral combination of decitabine and cedazuridine (a chemotherapy treatment) to assess its safety and pharmacokinetics in people with cancer. It targets individuals with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or solid tumors, particularly those with liver issues. Participants are divided into groups based on liver function to compare results. Ideal candidates are those with cancer and liver impairment who have no other standard treatment options available. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial requires that you stop taking azacitidine or decitabine at least 4 weeks before screening and any investigational or certain other therapies at least 2 weeks before the first dose. Some medications, like those for MDS, must be stopped at least 1 week before the first dose, but short-term use of certain medications like G-CSF is allowed with a doctor's guidance.

Is there any evidence suggesting that oral decitabine and cedazuridine is likely to be safe for humans?

Earlier research has shown that taking decitabine and cedazuridine orally is safe for patients. For instance, in a study involving patients with myelodysplastic syndromes (MDS), most side effects were mild and manageable. The most common issue was a drop in blood cell counts, which is expected with this type of treatment. Another study found that taking these medications orally worked almost as well in the body as the traditional IV method, suggesting they are well-tolerated. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about oral Decitabine combined with Cedazuridine for treating Myelodysplastic Syndrome because it offers a new approach compared to traditional treatments, which usually involve injectable hypomethylating agents like azacitidine or decitabine. This combination is unique because it can be taken orally, which could improve patient convenience and adherence to the treatment regimen. Additionally, Cedazuridine acts as an inhibitor that enhances the bioavailability of Decitabine, potentially increasing its effectiveness while minimizing the need for intravenous administration. This innovative delivery method could transform how patients manage their treatment and improve overall outcomes.

What evidence suggests that oral decitabine and cedazuridine might be an effective treatment for myelodysplastic syndrome?

Research has shown that taking decitabine and cedazuridine orally is as effective and safe as receiving it through an IV for treating conditions like myelodysplastic syndrome (MDS). Studies have found that the oral version provides approximately 98.93% of the drug exposure level of the IV form, indicating similar efficacy. Patients report that the oral medication minimally interferes with daily activities and can improve quality of life compared to IV treatments. Overall, this treatment offers a promising alternative to injections, with comparable effectiveness. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of blood cancer or solid tumors that are advanced and can't be removed by surgery. They should not have other treatment options available. Participants need to understand the study, follow its procedures, and give informed consent. They must have a specific level of platelets and white blood cells, an ECOG performance status from 0 to 2, and either normal liver function or moderate to severe hepatic impairment.

Inclusion Criteria

I understand the study, its risks, and can follow the treatment plan.

Platelet count ≥ 25,000/μL;

Absolute neutrophil count (ANC) ≥ 100 cells/μL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple oral doses of decitabine and cedazuridine for pharmacokinetic and safety evaluation

8 weeks

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Decitabine and Cedazuridine

Trial Overview The trial is testing ASTX727—a combination of oral decitabine (35 mg) and cedazuridine (100 mg)—in patients with varying levels of liver function. It's in Phase 1b, focusing on how the body processes the drug (pharmacokinetics) and safety over approximately up to an eight-week period per participant.

How Is the Trial Designed?

Group I: Group C: Severe hepatic impairment Experimental Treatment 1 Intervention

Cancer participants with severe hepatic impairment (\>3X ULN; any AST level)

Group II: Group B: Moderate hepatic impairment Experimental Treatment 1 Intervention

Cancer participants with moderate hepatic impairment \[total bilirubin \>1.5X - 3X upper limit of normal (ULN); any aspartate aminotransferase (AST) level\]

Group III: Group A: Normal hepatic function Active Control 1 Intervention

Cancer participants with normal hepatic function (total bilirubin ≤ULN; AST ≤ULN)

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Astex Pharmaceuticals, Inc.

Lead 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

Published Research Related to This Trial

Luspatercept has shown significant efficacy in treating low-risk myelodysplastic syndromes (MDS), with 63% of patients experiencing hematological improvement and 38% achieving transfusion independence in clinical trials.

Oral decitabine combined with oral cedazuridine has demonstrated pharmacological equivalence to intravenous decitabine, achieving overall response rates of 60% and 43% in phase 2 and 3 trials for high-risk MDS, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatment for myelodysplastic syndromes: luspatercept and oral hypomethylating agents]. Usuki, K.[2022]

Inqovi, a combination of decitabine and cedazuridine, was approved by the FDA for treating myelodysplastic syndromes (MDS) based on a phase III study involving 133 adults, showing similar effectiveness to intravenous decitabine.

The treatment demonstrated a complete remission rate of 21% in one study and 18% in another, with a median duration of remission lasting around 7.5 to 8.7 months, while adverse reactions were consistent with those seen in IV decitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Decitabine and Cedazuridine Tablets for Myelodysplastic Syndromes. Kim, N., Norsworthy, KJ., Subramaniam, S., et al.[2023]

The fixed-dose oral combination of decitabine and cedazuridine (Inqovi®) has been approved for treating myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), enhancing the oral bioavailability of decitabine through the inhibition of cytidine deaminase by cedazuridine.

Decitabine is already an established treatment for MDS and CMML, and the combination therapy has shown promise in ongoing clinical studies for other cancers like acute myeloid leukaemia (AML), glioma, and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine: First Approval. Dhillon, S.[2021]

The combination of oral cedazuridine and decitabine (C-DEC) has been shown to have a similar pharmacokinetic and pharmacodynamic profile to parenteral decitabine, making it a promising alternative for treating higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

Phase 2 and phase 3 clinical trials confirmed the bioequivalence of C-DEC to parenteral decitabine, leading to FDA approval for its use in intermediate/high-risk MDS and CMML, highlighting its efficacy and safety as an oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies. Patel, AA., Cahill, K., Saygin, C., et al.[2023]

In a phase 1 study involving 44 patients with myelodysplastic syndromes or chronic myelomonocytic leukaemia, the combination of oral decitabine and the CDA inhibitor cedazuridine successfully increased the bioavailability of decitabine, achieving pharmacokinetics similar to intravenous administration without increasing toxicity.

The study demonstrated that oral decitabine combined with cedazuridine produced effective dose-dependent demethylation and clinical responses comparable to intravenous decitabine, suggesting it could be a viable alternative treatment for myeloid disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Savona, MR., Odenike, O., Amrein, PC., et al.[2019]

The phase 2 study found that oral cedazuridine/decitabine (100 mg/35 mg) provided similar systemic exposure and DNA demethylation compared to standard IV decitabine (20 mg/m2) in patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, indicating comparable efficacy.

Clinical responses were observed in 60% of patients, with 21% achieving a complete response, while the most common serious side effects included neutropenia (46%) and thrombocytopenia (38%), highlighting the treatment's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Garcia-Manero, G., Griffiths, EA., Steensma, DP., et al.[2021]

Decitabine/cedazuridine (DEC-C) is the first oral hypomethylating agent approved in Canada for treating myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML), showing a median overall survival of 21.6 months in a real-world study of 769 patients.

The treatment demonstrated a median progression-free survival of 10.7 months, indicating its potential as an effective and convenient alternative to traditional parenteral therapies, especially for older patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada. Yun, JP., Ding, PQ., Dolley, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11292726/

Patients' perspectives on oral decitabine/cedazuridine for ... Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting ...

2. nature.com nature.com/articles/s41408-025-01245-5

Oral decitabine cedazuridine with and without venetoclax ... According to a recent systematic review, patients with higher-risk MDS treated with single-agent azacytidine experienced a complete remission ( ...

3. taihooncology.com taihooncology.com/us/news/2023-12-10_ash_data_presentation_us_real_world_study/

Dec. 10, 2023 “Previous studies have shown that oral decitabine and cedazuridine provides comparable safety and efficacy to parenteral HMAs,1,2,3 and what we ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38135371/

Oral decitabine-cedazuridine versus intravenous ... Primary endpoint of total exposure of oral decitabine-cedazuridine versus intravenous decitabine was 98·93% (90% CI 92·66-105·60), indicating equivalent ...

5. onclive.com onclive.com/view/oral-decitabine-cedazuridine-is-a-game-changer-for-mds-and-cmml-treatment

Oral Decitabine-Cedazuridine Is a Game Changer for ... Critically, the primary end point of total drug exposure was met, with the oral formulation achieving 98.93% (90% CI, 92.66%-105.60%) of the IV ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6709/528741/Oral-Decitabine-Cedazuridine-Adverse-Effects-and

Oral Decitabine-Cedazuridine: Adverse Effects and ... Of these patients, 58 (90.6%) had myelodysplastic syndromes (MDS), categorized as follows: 15 (25.9%) with low or very low risk, 15 (25.9%) with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023012065

MDS-641 Randomized Phase 1-2 Study to Assess Safety ... MDS-641 Randomized Phase 1-2 Study to Assess Safety and Efficacy of Low-Dose (LD) Oral Decitabine/Cedazuridine (ASTX727) in Lower-Risk Myelodysplastic Syndromes ...