Oral Azacitidine for Blood Cancers

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Must be taking: Oral azacitidine

Must not be taking: Injectable azacitidine

Disqualifiers: Pregnancy, Lactation, Prior chemotherapy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5 years

4 Participants Needed

Trial Summary

What is the purpose of this trial?

Rollover study supporting hematological disorder indications from Celgene sponsored CC-486 (oral azacitidine) protocols eligible for participation in the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use drugs that are prohibited during the study. It's best to discuss your current medications with the study team to see if any are prohibited.

What data supports the effectiveness of the drug CC-486 (oral azacitidine) for blood cancers?

CC-486 has been shown to improve overall survival in older patients with acute myeloid leukemia who are in complete remission and cannot complete intensive therapy. In patients with lower-risk myelodysplastic syndromes, CC-486 led to a response in 36-41% of patients, with some achieving independence from blood transfusions. ^{1 2 3 4 5}

Is oral azacitidine (CC-486) safe for humans?

Oral azacitidine (CC-486) has been generally well-tolerated in clinical trials, but common side effects include gastrointestinal issues (like nausea and diarrhea) and blood-related problems (like low white blood cell counts). Some patients experienced fatigue and pneumonia, and those with liver issues may need careful monitoring. ^{1 4 5 6 7}

How is oral azacitidine different from other drugs for blood cancers?

Oral azacitidine (CC-486) is unique because it is taken by mouth, allowing for extended dosing schedules that increase exposure to cancer cells, which is not possible with the injectable form. This oral formulation provides a convenient option for maintenance therapy in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), potentially improving overall survival and treatment outcomes. ^{1 2 4 6 8}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for patients who have participated in previous CC-486 (oral azacitidine) studies for blood cancers and continue to meet those trials' criteria. They should benefit from ongoing treatment, adhere to the study's schedule, and use effective contraception if of childbearing potential.

Inclusion Criteria

Subjects must satisfy the following criteria to participate in the Survival Follow-up phase:

Understand and voluntarily sign an informed consent document prior to any study related assessments or procedures being conducted.

I am a woman who can have children and meet specific health conditions.

Exclusion Criteria

Pregnant or lactating females.

Subjects have met one or more criteria for discontinuation as stipulated in the parent oral azacitidine study.

I am not taking any medications that are not allowed in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants continue receiving CC-486 (oral azacitidine) at the same dose, schedule, and frequency as in the parent study to evaluate long-term safety

Approximately 5 years

Follow-up

Participants' survival will be followed if required by the parent CC-486 study protocol

Up to 5 years

Treatment Details

Interventions

• CC-486

Trial Overview The study tests the long-term safety of CC-486 (oral azacitidine), a drug used for treating hematological disorders. It's a rollover study, meaning it continues treatment from previous trials with this medication.

Participant Groups

Group I: Oral Azacitidine (CC-486) Experimental Treatment 1 Intervention

This study is an open-label, single-arm study and is divided into the screening period, treatment period and follow-up period. It is intended to evaluate the long-term safety of CC-486 and is to be taken at the same dose, schedule and frequency used from the last dose of CC-486 given in the parent study.

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

Oral azacitidine (CC-486) has been shown to improve overall survival as maintenance therapy for older patients with acute myeloid leukemia who are in complete remission, highlighting its efficacy in this specific patient population.

The combination of decitabine and cedazuridine (ASTX727) is approved for treating adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia, particularly those with intermediate-1 or higher risk, indicating its targeted therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. Kipp, D., H Wei, A.[2022]

Oral azacitidine (Onureg, CC-486) has been approved by the FDA for the continued treatment of adult patients with acute myeloid leukemia (AML) who are in complete remission but cannot undergo intensive curative therapy, showing a significant improvement in overall survival compared to placebo in a trial with older adults (≥ 55 years).

While CC-486 is effective, it is associated with gastrointestinal toxicities, fatigue, and pneumonia, and caution is advised regarding dosing, especially in patients with liver issues, as its pharmacokinetics differ from other azacitidine formulations, which could lead to serious risks if substituted incorrectly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Oral Azacitidine for Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy. Jen, EY., Wang, X., Li, M., et al.[2023]

Extended dosing of CC-486 (oral azacitidine) in patients with myelodysplastic syndromes and acute myeloid leukemia showed significant reductions in global DNA methylation, indicating sustained epigenetic activity throughout the treatment cycle.

The study involved 59 patients and demonstrated that both 300mg once-daily and 200mg twice-daily dosing schedules effectively maintained hypomethylation, with greater reductions in methylation correlating with hematologic responses, suggesting a potential link between epigenetic changes and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. Laille, E., Shi, T., Garcia-Manero, G., et al.[2018]

Oral azacitidine (Oral-AZA) has been approved for treating adult patients with acute myeloid leukemia (AML) in first complete remission, showing a significant median overall survival advantage of 9.9 months compared to placebo in the QUAZAR AML-001 trial.

Oral-AZA offers a more convenient dosing regimen than injectable azacitidine, allowing for extended treatment cycles, which may improve patient adherence and outcomes in maintenance therapy for AML and potentially in myelodysplastic syndromes (MDS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies. Garcia-Manero, G., Döhner, H., Wei, AH., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer. [2021]

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

The path to approval for oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes. [2022]

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

Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. [2022]

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

Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. [2018]

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

FDA Approval Summary: Oral Azacitidine for Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy. [2023]

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

Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies. [2018]

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

Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. [2021]

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

Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies. [2022]