Oral Azacitidine for Leukemia

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: John Reneau

Must not be taking: 5-azacytidine, Decitabine

Disqualifiers: Active infection, HIV, Hepatitis B, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4-12 months

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies the best dose and effects of oral azacitidine in patients with T-cell large granular lymphocytic leukemia that has come back or did not respond to previous treatments. Azacitidine is a chemotherapy drug that stops cancer cells from growing, dividing, or spreading.

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

The trial requires that you stop any current treatments for at least 14 days or 5 half-lives (the time it takes for the drug's concentration to reduce by half), whichever is longer, before starting the trial. However, if you are on stable, low-dose prednisone (10 mg or less) for certain conditions, you may continue it.

What data supports the effectiveness of the drug Oral Azacitidine for Leukemia?

Azacitidine, a component of Oral Azacitidine, has been shown to be effective in treating higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), as it can prolong survival and improve remission rates compared to conventional care. It is well-tolerated and has been used successfully in real-world settings for these conditions. ^{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 studies indicating it is well-tolerated in patients with conditions like myelodysplastic syndromes and acute myeloid leukemia. While some side effects may occur, the overall safety profile is acceptable, especially in older patients. ^{1 2 3 4 6}

What makes the drug Oral Azacitidine unique for treating leukemia?

Oral Azacitidine is unique because it offers a convenient oral administration compared to the traditional subcutaneous or intravenous injections, potentially reducing side effects and improving patient comfort. This oral form has been developed to overcome previous challenges with rapid breakdown in the body, making it a novel option for patients with leukemia. ^{2 3 4 5 7}

Research Team

Jonathan E. Brammer, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults with relapsed or refractory T-cell large granular lymphocytic leukemia who need treatment and have not used certain drugs like 5-azacytidine. They must be able to consent, have a decent performance status, meet specific blood count criteria, agree to use birth control, and be off previous treatments for a set time. Those with active infections or on immune-suppressive therapy (beyond low-dose prednisone) are excluded.

Inclusion Criteria

My hemoglobin is below 10 g/dL and I feel very tired.

I have been diagnosed with a specific type of leukemia (T-LGLL or NK LGL) based on my blood cell counts and genetic tests.

I need regular blood transfusions for my anemia.

Exclusion Criteria

I have another cancer, but it's related to my T-LGLL condition.

Positive pregnancy test

I have previously used 5-azacytidine or decitabine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive oral azacitidine on days 1-14 of a 28-day cycle for a minimum of 4 cycles. Patients with a response continue treatment for up to 12 months.

4-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Oral Azacitidine

Trial Overview The trial is testing oral Azacitidine to find the best dose and assess its benefits/side effects in patients whose T-cell large granular lymphocytic leukemia has returned after treatment or didn't respond at all. It's a phase I/II study which means they're looking at safety as well as how well it works.

Participant Groups

Group I: Treatment (Oral Azacitidne) Experimental Treatment 1 Intervention

Patients will receive CC-486 orally (PO) D1-14 of a 28-day cycle, in a similar fashion to the QUAZAR study for a minimum of 4 cycles. Patients that achieve a response (CR or PR) will remain on study for a maximum of 12 months. Patients without a response at 4 months will come off the study.

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?

John Reneau

Lead Sponsor

Trials

4

Recruited

90+

Jonathan Brammer

Lead Sponsor

Trials

2

Recruited

60+

Bristol-Myers Squibb

Industry 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 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]

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]

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 (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]

In a Phase II study involving 20 elderly patients (median age 76) with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), a combination treatment of hydroxyurea, azacitidine, and low-dose gemtuzumab ozogamicin resulted in a high complete remission rate of 70%.

The treatment was found to be safe, with only one early death (5%) due to disease progression, and the median survival for patients was 10 months, indicating that this regimen could be a promising option for this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Nand, S., Godwin, J., Smith, S., et al.[2019]

Azacitidine, an antileukemia drug, has shown survival benefits in patients with high-risk myelodysplastic syndrome (MDS) and is effective in treating acute myelogenous leukemia (AML).

A pilot study with four subjects demonstrated that an oral formulation of azacitidine is bioavailable, with a mean bioavailability of 17.4% compared to subcutaneous administration, and was well-tolerated without severe toxicities, suggesting it warrants further investigation in phase 1 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot pharmacokinetic study of oral azacitidine. Garcia-Manero, G., Stoltz, ML., Ward, MR., et al.[2023]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

6. United States pubmed.ncbi.nlm.nih.gov

Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. [2019]

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

A pilot pharmacokinetic study of oral azacitidine. [2023]