Oral Azacitidine for Myelodysplastic Syndrome

Not currently recruiting at 126 trial locations

Overseen By First line of the email MUST contain NCT # and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Azacitidine, Decitabine

Disqualifiers: Hypoplastic MDS, MDS-EB2, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of oral azacitidine for individuals with myelodysplastic syndrome (MDS), a condition where the bone marrow fails to produce enough healthy blood cells. The study includes different groups, with some receiving varying doses of the drug and others receiving a placebo (a pill with no active drug). Individuals with low to intermediate risk MDS, who have not previously received similar treatments, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that oral azacitidine is generally safe for people with myelodysplastic syndrome (MDS). Studies have found that patients with lower to intermediate risk of MDS handle this treatment well. Specifically, two lower doses of oral azacitidine, 200 mg and 300 mg, have been found to be safe, with no major differences in side effects between these doses.

Previous studies report that common side effects may include mild to moderate stomach issues, such as nausea or diarrhea. However, these side effects are usually manageable. Overall, most patients tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Oral Azacitidine is unique because it offers a convenient oral administration for myelodysplastic syndrome (MDS), unlike the standard of care treatments like injectable azacitidine or decitabine. This new delivery method could greatly improve patient comfort and adherence, as it eliminates the need for regular hospital visits for injections. Additionally, oral azacitidine maintains the same mechanism of action, disrupting abnormal DNA methylation, which is essential for tackling the root cause of MDS. Researchers are excited because this approach might combine the effectiveness of existing therapies with enhanced ease of use, potentially leading to better overall outcomes for patients.

What evidence suggests that oral azacitidine might be an effective treatment for myelodysplastic syndrome?

Research has shown that oral azacitidine, which participants in this trial may receive, offers promising results for people with myelodysplastic syndrome (MDS). One study found that it significantly reduced the need for red blood cell transfusions, meaning patients required fewer transfusions. Many patients with anemia also experienced improved blood counts. Azacitidine has been linked to longer survival in patients with higher-risk MDS, suggesting it may help slow the disease's progression. These findings highlight its potential as an effective treatment for MDS. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for people with a specific blood disorder called Myelodysplastic Syndrome (MDS) that's not too advanced. They should be able to do daily activities on their own or with little help, and haven't been treated with drugs like azacitidine before. People who've had other cancers must be in good health and not have received cancer treatment recently.

Inclusion Criteria

I am able to care for myself and perform daily activities.

My MDS is classified as low or intermediate risk, with an IPSS-R score between 1.5 and 4.5.

Exclusion Criteria

I have been diagnosed with a type of blood disorder known as MDS-EB2.

My bone marrow is very underactive, with cellularity 10% or less.

I have been treated with azacitidine, decitabine, or similar drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral azacitidine or placebo plus best supportive care

24 weeks

6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Long-term follow-up

Participants are monitored for long-term outcomes such as overall survival and event-free survival

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Oral Azacitidine
• Placebo for Oral Azacitidine

Trial Overview The study tests if oral azacitidine helps patients with low- to intermediate-risk MDS better than a placebo. Both groups also get the best supportive care available. The main goal is to see which group has better health outcomes.

How Is the Trial Designed?

Group I: Part II - Placebo Experimental Treatment 1 Intervention

Group II: Part II - Oral-Aza (RP3D) Experimental Treatment 1 Intervention

RP3D: Recommended Phase 3 Dose

Group III: Part I - Oral-Aza (Dose 2) Experimental Treatment 1 Intervention

Group IV: Part I - Oral-Aza (Dose 1) Experimental Treatment 1 Intervention

Oral Azacitidine is already approved in United States, European Union for the following indications:

Approved in United States as Vidaza for:

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia

Approved in United States as Onureg for:

• Acute Myeloid Leukemia

Approved in European Union as Vidaza for:

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Azacitidine is an approved treatment for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), showing benefits even in patients with higher blast counts, as demonstrated in recent phase III trials.

Oral azacitidine (CC-486) has shown promising biological activity and tolerability in early studies, potentially offering a more convenient treatment option for patients with MDS and AML, with ongoing investigations into extended dosing schedules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cogle, CR., Scott, BL., Boyd, T., et al.[2023]

Azacitidine was approved by the FDA for treating all subtypes of myelodysplastic syndrome (MDS) based on a randomized controlled trial showing a 16% overall response rate, with sustained responses lasting up to 17 months.

The treatment demonstrated a favorable safety profile, with no deaths attributed to azacitidine, although common side effects included gastrointestinal issues and hematologic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Kaminskas, E., Farrell, AT., Wang, YC., et al.[2013]

In a real-life study of 49 patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), azacitidine demonstrated a clinically acceptable safety profile, with 67.3% of patients experiencing treatment-related adverse events.

Efficacy results showed that 41.4% of MDS and CMML patients achieved a complete or partial response, and 43.8% of transfusion-dependent patients became transfusion-independent, with a median overall survival of 490 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey. Beguin, Y., Selleslag, D., Meers, S., et al.[2015]

In a study of 149 patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML), azacitidine treatment resulted in a median progression-free survival (PFS) of 10.9 months and an overall survival (OS) of 14.1 months, demonstrating its effectiveness in a real-world clinical setting.

The safety profile of azacitidine was consistent with previous clinical trials, and factors such as Eastern Cooperative Oncology Group (ECOG) performance status and red blood cell transfusion prior to treatment were identified as predictive factors for better PFS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Wehmeyer, J., Zaiss, M., Losem, C., et al.[2019]

Azacitidine (Vidaza) is the only drug approved in the EU that significantly prolongs survival in adults with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), making it a crucial treatment option for patients not eligible for stem cell transplantation.

The treatment is associated with a lower risk of AML progression and higher rates of remission and blood transfusion independence, while maintaining an acceptable safety profile, with peripheral cytopenias being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Keating, GM.[2021]

Azacitidine is an effective and well-tolerated treatment for patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), including older patients who are ineligible for stem cell transplants, as demonstrated in pivotal phase 3 trials.

It is the only approved hypomethylating agent that has been shown to prolong overall survival compared to conventional care, making it the recommended first-line treatment for most patients with higher-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine: A Review in Myelodysplastic Syndromes and Acute Myeloid Leukaemia. Scott, LJ.[2022]

The Vidaza Access Program in Belgium successfully facilitated access to azacitidine treatment for 175 patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) by streamlining the approval process for patient dossiers.

Out of the 175 patient dossiers submitted, 163 were approved by Celgene, demonstrating the program's effectiveness in ensuring timely treatment initiation without financial risk to hospitals, which is crucial for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. Meers, S., Selleslag, D., Potier, H., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3627328/

Azacitidine in the management of patients with ... Azacitidine has demonstrated significant and clinically meaningful prolongation of survival in higher-risk patients with MDS and has changed the natural history ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6509

Preliminary safety and efficacy of oral azacitidine (Oral-AZA ... Six pts in each dose group achieved HI-E. Among mITT pts with anemia at BL, 6/19 (31.6%) pts in the 200 mg and 5/18 (27.8%) pts in the 300 mg ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023021973

Real-world Effectiveness of Azacitidine in Treatment-Naive ... The real-world outcomes from AZA have been lower than expected with a registry of the Spanish cooperative group on MDS reporting a median OS of 13.4 months from ...

4. hematologyadvisor.com hematologyadvisor.com/reports/myelodysplastic-syndrome-mds-azacitidine-improve-outcomes-treatment/

5-Day Azacitidine May Improve Outcomes Compared With ... Multivariate analysis among patients with transfusion-dependence suggested that 5-day azacitidine improved OS outcomes compared with 3-day ...

5. ashpublications.org ashpublications.org/ashclinicalnews/news/7971/Safety-of-Oral-Azacytidine-in-Patients-With-Lower

Safety of Oral Azacytidine in Patients With Lower-Risk MDS ... This treatment significantly improved the rate of red blood cell count transfusion independence versus placebo and led to durable improvements ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2948932/

Safety and efficacy of azacitidine in myelodysplastic ... The overall response observed in patients with low-risk MDS receiving azacitidine was 59% (9% CR, 18% PR, and 32% hematological improvement), with an overall ...

7. cancernetwork.com cancernetwork.com/view/safety-profile-of-oral-azacitadine-remains-consistent-in-lower-risk-mds

Safety Profile of Oral Azacitadine Remains Consistent in ... The safety profile of oral azacitadine was shown to be similar across the 200-mg and 300-mg arms in patients with lower- to intermediate-risk MDS.

8. onuregpro.com onuregpro.com/efficacy

ONUREG® (azacitidine) Efficacy Profile | for HCPs Median overall survival was ~4 years in patients with an NPM1 mutation treated with ONUREG ... Analysis limitations: Results should be interpreted with caution, ...