Oral Azacitidine for Acute Myeloid Leukemia

(REMAIN1 Trial)

Overseen By Massey IIT Research Operations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Virginia Commonwealth University

Must not be taking: Azacitidine

Disqualifiers: FLT3 mutation, CNS involvement, 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: Unknown

Duration: 4 months

12 Participants Needed

Trial Summary

What is the purpose of this trial?

Test feasibility of an oral maintenance strategy for transplant eligible AML patients in first CR who are medically underserved or have a disadvantage in the CDC SDOH domains

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 study team or your doctor.

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

Research shows that azacitidine, the active ingredient in Oral Azacitidine, has been effective in improving survival in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In a trial, oral azacitidine significantly increased overall survival by nearly 10 months compared to a placebo in patients with AML. ^{1 2 3 4 5}

Is oral azacitidine safe for humans?

Azacitidine, also known as Vidaza, has been studied for safety in patients with conditions like myelodysplastic syndromes and acute myeloid leukemia. It is generally well-tolerated, with studies showing it to be safe in these patient groups, including older adults. ^{1 2 5 6 7}

What makes Oral Azacitidine unique for treating acute myeloid leukemia?

Oral Azacitidine is unique because it is an oral formulation that allows for convenient extended dosing, which is not feasible with the injectable form. It has shown a significant survival advantage in patients with acute myeloid leukemia in remission, offering a more accessible and potentially more effective maintenance therapy option. ^{1 2 8 9 10}

Research Team

Keri Maher

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

This trial is for adults over 18 with Acute Myeloid Leukemia (AML) who've finished initial therapy and are in remission but face health disparities. They must be able to take pills, have decent organ function, and not have certain AML types or mutations. Women must avoid pregnancy during the study.

Inclusion Criteria

I can take pills by mouth.

I can care for myself but may not be able to do heavy physical work.

I finished my last treatment less than 4 months ago.

Exclusion Criteria

I have been treated with oral azacitidine before.

History of hypersensitivity or allergic reaction to azacitidine or its components

My brain or spinal cord cancer is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral azacitidine 300 mg once daily for 14 days in a 28-day cycle

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Treatment Details

Interventions

• Oral Azacitidine

Trial Overview The trial tests if transplant-eligible AML patients in first complete response can maintain their disease status using oral Azacitidine while facing social and health inequalities. It's about finding out if this pill form of treatment works for those less served by healthcare.

Participant Groups

Group I: Oral Azacitidine Experimental Treatment 1 Intervention

Starting dose is oral azacitidine 300 mg orally once daily with or without food days 1-14 in a 28-day cycle

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?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Findings from Research

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]

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 the AZA-001 trial, azacitidine significantly improved survival in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia, with 91 out of 179 patients responding to treatment after a median of 14 cycles.

Continued treatment with azacitidine beyond the first response led to an improved response category in 48% of patients, suggesting that ongoing therapy can enhance clinical benefits for those who initially respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Silverman, LR., Fenaux, P., Mufti, GJ., et al.[2022]

Oral azacitidine significantly improves overall survival in patients with acute myeloid leukaemia (AML) after induction therapy, with a median survival gain of 9.9 months compared to placebo, as shown in the QUAZAR AML-001 trial involving a substantial number of participants.

The cost-effectiveness analysis indicated that oral azacitidine has a probabilistic incremental cost-effectiveness ratio (ICER) of approximately £32,480 per quality-adjusted life year (QALY) gained compared to watch-and-wait plus best supportive care, making it a recommended option for maintenance treatment in eligible AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Azacitidine for Maintenance Treatment of Acute Myeloid Leukaemia After Induction Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Witlox, W., Grimm, S., Howick, J., et al.[2023]

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 maximum-tolerated dose (MTD) of oral azacitidine was determined to be 480 mg, with common side effects including diarrhea, nausea, and febrile neutropenia, indicating a manageable safety profile for patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML).

Oral azacitidine showed significant clinical activity, achieving a 35% overall response rate in previously treated patients and a 73% response rate in previously untreated patients, demonstrating its efficacy in reducing DNA methylation and improving hematologic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. Garcia-Manero, G., Gore, SD., Cogle, C., et al.[2022]

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, 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]

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]

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

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

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

Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. [2022]

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

Oral Azacitidine for Maintenance Treatment of Acute Myeloid Leukaemia After Induction Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. [2023]

5. 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]

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

Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

A pilot pharmacokinetic study of oral azacitidine. [2023]

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

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

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

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