Oral Azacitidine for Leukemia

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose and evaluate the benefits and side effects of oral azacitidine, a chemotherapy drug, for individuals with T-cell large granular lymphocytic leukemia. The focus is on patients whose cancer has relapsed or is refractory to previous therapies. Participants will take the medication orally over a specific cycle, as in past studies, and continue if they show improvement. The trial seeks individuals with T-LGLL who require treatment due to symptoms like severe anemia or frequent infections and have not succeeded with at least one prior treatment. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that oral azacitidine is likely to be safe for humans?

Research has shown that oral azacitidine, a type of chemotherapy, is safe and effective for treating various cancers. In previous studies, about 12% of patients experienced febrile neutropenia, a condition involving fever and low white blood cell counts. This weakens the immune system, increasing infection risk. Some patients required medication dose adjustments due to low levels of neutrophils and platelets, which help fight infections and stop bleeding.

Despite these side effects, oral azacitidine offers potential benefits. Real-world studies indicate that it can extend patient survival and prevent cancer recurrence. However, these studies also highlight the importance of monitoring side effects and adjusting treatment as needed to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Oral Azacitidine is unique because it offers a new way to deliver treatment for leukemia through an oral form, unlike the standard chemotherapy options, which are typically administered via injection or infusion. This oral delivery method can make treatment more convenient and less invasive for patients. Additionally, Oral Azacitidine is based on Azacitidine, a well-known chemotherapy drug, but its oral form could potentially improve patient compliance and quality of life by making it easier to take at home. Researchers are excited because this could mean more accessible and patient-friendly treatment options without compromising effectiveness.

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

Research has shown that oral azacitidine, the treatment under study in this trial, can help treat certain types of leukemia. Studies have found that this medication can extend remission, meaning the cancer remains inactive for a longer period. Specifically, patients with acute myeloid leukemia (AML) who took oral azacitidine stayed in remission longer than those who did not. Additionally, about 75% of patients lived for at least a year after starting oral azacitidine. These results suggest that oral azacitidine may benefit individuals with relapsed or hard-to-treat T-cell large granular lymphocytic leukemia. ^{1 2 5 6 7}

Who Is on the Research Team?

Jonathan E. Brammer, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40233158/

Real-world treatment patterns and outcomes with oral ...

Rates of real-world relapse-free survival and overall survival at 12 months from oral-AZA initiation were 66.9% and 74.5%, respectively. During ...

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ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/2425/531542/Real-World-Treatment-Patterns-and-Outcomes-with

Real-World Treatment Patterns and Outcomes with Oral ...

After a median follow-up of 12.8 months (mo), treatment with Oral-AZA was still ongoing for 137/208 pts (66%). The median duration of Oral-AZA ...

3.

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, ...

4.

healthtree.org

healthtree.org/aml/community/articles/outcomes-oral-azacitidine-secondary-aml

Outcomes from Oral Azacitidine Maintenance Therapy

AML-MRC patients who took oral azacitidine had a longer time in remission of 7.5 months, compared to the placebo group's 3.7 months. In ...

5.

rtihs.org

rtihs.org/publications/real-world-treatment-patterns-and-outcomes-oral-azacitidine-maintenance-therapy

Real-World treatment patterns and outcomes with oral ...

Six- and 12-mo overall survival rates from Oral-AZA initiation were 89.0% (standard error [SE]:3.1) and 74.5% (SE:5.0), respectively. Six- and ...

6.

onuregpro.com

onuregpro.com/safety

ONUREG® (azacitidine) Safety Info | for HCPs

Febrile neutropenia occurred in 12%. A dose reduction was required for 7% and 2% of patients due to neutropenia and thrombocytopenia. Less than 1% of patients ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497124051784

Real-World Treatment Patterns and Outcomes with Oral ...

Oral-AZA maintenance therapy significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with placebo for patients (pts) with acute ...