Oral Azacitidine for Myelodysplastic Syndrome

Recruiting at 114 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

230 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of oral azacitidine in participants with low to intermediate International Prognostic Scoring System Revised (IPSS-R) myelodysplastic syndrome (MDS).

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.

What data supports the effectiveness of the drug Oral Azacitidine for Myelodysplastic Syndrome?

Azacitidine, a component of Oral Azacitidine, is shown to be effective in treating higher-risk myelodysplastic syndromes (MDS) by improving survival compared to conventional care, as evidenced by multiple studies and real-world data. ^{1 2 3 4 5}

Is Oral Azacitidine safe for humans?

Azacitidine, also known as Vidaza, has been shown to be generally safe in humans, with common side effects including nausea, vomiting, diarrhea, and low blood cell counts. Serious side effects like liver function abnormalities and renal failure have been reported but are less common. No deaths have been directly attributed to azacitidine in studies. ^{1 2 3 5 6}

What makes the drug Oral Azacitidine unique for treating Myelodysplastic Syndrome?

Oral Azacitidine is unique because it offers a convenient oral administration compared to the traditional injectable form, potentially improving patient comfort and adherence to treatment. It also allows for flexible dosing schedules, which can be beneficial for long-term management of Myelodysplastic Syndrome. ^{1 5 6 7 8}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 (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]

References

1. England 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). [2019]

2. England pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

3. England 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. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Practical use of azacitidine in higher-risk myelodysplastic syndromes: an expert panel opinion. [2013]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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