Oral Azacitidine for Blood Cancers

No longer recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called oral azacitidine (also known as CC-486) to treat blood cancers by assessing its long-term safety. Participants have already taken this medication in a previous study and responded well. It suits those who have previously received this treatment and continue to benefit from it. The main goal is to monitor the medication's ongoing safety and effectiveness. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that oral azacitidine (CC-486) is likely to be safe for humans?

Studies have shown that oral azacitidine (CC-486) is generally well-tolerated in patients with blood cancers. One study found that combining CC-486 with another treatment was safe for patients. The most common serious side effects involved blood cells, such as anemia (low red blood cells), thrombocytopenia (low blood platelets), and neutropenia (low white blood cells). These side effects occurred in about 11.5% of patients for anemia and thrombocytopenia, and 7.7% for neutropenia.

These findings suggest that while some risks exist, CC-486 has been used safely in past studies. However, researchers continue to study the treatment's safety for other blood conditions. Always consult a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CC-486, an oral form of azacitidine, because it offers a new way to manage blood cancers, such as myelodysplastic syndromes and acute myeloid leukemia. Unlike traditional treatments that are often given intravenously, CC-486 can be taken orally, making it more convenient for patients and potentially improving adherence to treatment. Additionally, this delivery method allows for continuous exposure to the drug, which might enhance its effectiveness in targeting cancer cells. Overall, CC-486 could simplify the treatment process while maintaining or even increasing its efficacy.

What is the effectiveness track record for oral azacitidine in treating blood cancers?

Research has shown that oral azacitidine (CC-486), the treatment under study in this trial, holds promise for treating blood cancers. One study found that patients with acute myeloid leukemia (AML) who took CC-486 lived for a median of 29.5 months. Another study reported that 56% of patients responded to the treatment, with some achieving undetectable cancer levels. For patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML), 21% experienced a complete disappearance of their cancer. These findings suggest that oral azacitidine could effectively manage these blood cancers. ^{3 6 7 8 9}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34758945/

Oral Azacitidine (CC-486) for the Treatment of Myeloid ... Regulatory approvals of Oral-AZA were based on outcomes from the randomized, phase III QUAZAR AML-001 trial, which showed a median overall survival advantage of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S215226502102070X

Oral Azacitidine (CC-486) for the Treatment of Myeloid ... Preliminary efficacy results from the phase 3 ASCERTAIN study in MDS and CMML (NCT03306264) showed a CR rate of 21% and an overall response rate of (CR + mCR + ...

3. taihooncology.com taihooncology.com/us/news/taiho-oncology-data-at-ash-annual-meeting-highlight-progress-in-oral-therapies-for-patients-with-blood-cancers/

Taiho Oncology Data at ASH Annual Meeting Highlight ... The median overall survival was 29.5 months, with overall response rate of 56% (11% complete response, 0% partial response, 34% marrow complete ...

4. ashpublications.org ashpublications.org/blood/article/139/8/1147/476663/Phase-1-study-of-oral-azacitidine-CC-486-plus-R

Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in ... Among the 59 patients evaluable for efficacy in both the escalation phase and expansion phase, the overall response rate (ORR) was 94.9% (95% CI ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01757535

Study Details | NCT01757535 | Efficacy of Oral Azacitidine ... This is an international, multicenter, placebo-controlled, Phase 3 study with a double-blind, randomized, parallel-group design in subjects with de novo AML.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01835587?intr=%22Cc-486%22&viewType=Table&rank=5

Safety Study of Oral Azacitidine (CC-486) as Maintenance ... The purpose of the study is to determine the maximal tolerated dose and schedule of CC-486, known as oral azacitidine, in patients with AML or MDS after ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4679081/

Oral Azacitidine (CC-486) for the Treatment of ... This review presents clinical data supporting the use of injectable azacitidine in myelodysplastic syndromes and acute myeloid leukemia

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118531153

Safety and Efficacy of Oral Azacitidine (CC-486) ... The most frequent (≥5%) grade 3/4 hematologic AEs in the QDx14d cohort were anemia (11.5%), thrombocytopenia (11.5%), and neutropenia (7.7%); ...

9. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(21)02070-X/fulltext

Oral Azacitidine (CC-486) for the Treatment of Myeloid ... Oral-AZA may be beneficial treatment for other hematologic malignancies such as MDS, but further clinical studies are needed to optimize ...