Azacitidine for Myeloid Leukemia After Stem Cell Transplant

Overseen By NALINI JANAKIRAMAN, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Henry Ford Health System

Must be taking: Azacitidine

Disqualifiers: HIV, Hepatitis, CNS leukemia, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests azacitidine, a drug that may help prevent a relapse of myeloid leukemia (a type of blood cancer) after a stem cell transplant. Researchers aim to determine if azacitidine can safely maintain donor cell levels in the body and reduce the chance of leukemia returning. Suitable patients have experienced a drop in donor cells after their transplant but have not had a full relapse. As a Phase 2 trial, this 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 requires that you stop any prior chemotherapy, radiotherapy, or other investigational therapy at least 2 weeks before starting the treatment. It does not specify about other medications, so you should discuss your current medications with the trial team.

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

Research has shown that azacitidine is generally well-tolerated by patients with acute myeloid leukemia (AML). Studies have examined its use after a stem cell transplant, where a patient receives blood-forming cells from a donor. These studies suggest that azacitidine can help strengthen the immune system without causing major side effects.

Earlier research indicated that patients using azacitidine as ongoing treatment after a transplant experienced good safety outcomes. They did not show a significant increase in serious side effects, suggesting that azacitidine may be a safe option for those who have had stem cell transplants.

While some risks exist, azacitidine has been used to treat other conditions, demonstrating a certain level of safety. However, consulting a healthcare provider for advice tailored to individual situations is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myeloid leukemia?

Unlike the standard treatments for myeloid leukemia, such as chemotherapy or targeted therapy, azacitidine is unique because it works as a hypomethylating agent. This means it targets the DNA of cancer cells in a way that can potentially reverse abnormal gene silencing, which is a different mechanism compared to traditional drugs. Researchers are excited about azacitidine because it offers promise in maintaining remission and preventing relapse after a stem cell transplant, an area where current options are limited. This could mean a significant improvement in long-term outcomes for patients with myeloid leukemia.

What evidence suggests that azacitidine might be an effective treatment for myeloid leukemia after stem cell transplant?

Research has shown that azacitidine, which participants in this trial will receive, is generally well tolerated by most patients with acute myeloid leukemia after a stem cell transplant. Studies have found that azacitidine can help increase regulatory T cells, which play a key role in managing the immune system. This is beneficial because it may help lower the chances of the cancer returning without raising the risk of graft-versus-host disease (GVHD), a condition where the transplanted cells attack the patient's body. In past patients, azacitidine resulted in complete remission in 24% of cases and partial remission in 14% of cases. These findings suggest that azacitidine could be a promising option for managing leukemia after a transplant. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with AML/MDS/MPN, CMML who've had a stem cell transplant and show any drop in donor chimerism. They must have stable blood counts, no severe GVHD or active infections, not be pregnant, agree to use contraception if capable of childbearing, and have good organ function.

Inclusion Criteria

I had a stem cell transplant and my recovery markers are within the required range.

I haven't had chemotherapy, radiotherapy, or experimental treatments in the last 2 weeks.

Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Exclusion Criteria

My brain leukemia is in remission for at least 2 months.

I have severe graft versus host disease.

I do not have HIV, hepatitis, or cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine post allogeneic stem cell transplant to manage donor chimerism

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine

Trial Overview The study tests azacitidine's ability to maintain donor chimerism after an allogeneic stem cell transplant in patients with certain myeloid cancers. The goal is to reduce cancer relapse without increasing graft versus host disease by administering azacitidine between day 30 and day 180 post-transplant.

How Is the Trial Designed?

Group I: AZA Experimental Treatment 1 Intervention

azacitidine

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Published Research Related to This Trial

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]

Azacitidine is effective for treating adult patients with acute myeloid leukemia (AML) who have 20%-30% blasts and multilineage dysplasia, significantly prolonging median overall survival compared to conventional care, as shown in the AZA-001 phase III trial.

The review also highlights the potential benefits of combining azacitidine with other treatments for AML, suggesting it may enhance patient outcomes further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine for the treatment of patients with acute myeloid leukemia with 20%-30% blasts and multilineage dysplasia. Font, P.[2017]

In a study of 1406 patients receiving azacitidine, the most common severe adverse events were hematologic, with grade 3-4 anemia occurring in 43.4% of patients, which was higher than reported in clinical trials.

Despite the high frequency of adverse events, treatment discontinuation due to these events was low (5.1%), indicating that with proper management, azacitidine can be safely administered to most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents-A Prospective Cohort Study of the AGMT Study-Group. Leisch, M., Pfeilstöcker, M., Stauder, R., et al.[2022]

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]

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 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 100 patients with acute myeloid leukemia (AML) treated with hypomethylating agents (HMA) like azacitidine and decitabine, 24% achieved a response, and the median overall survival (OS) was 6.5 months, indicating some efficacy as salvage therapy.

Patients with secondary AML (sAML) had a significantly better median OS of 12.3 months compared to 6.1 months for those with de novo AML, suggesting that HMA may be particularly beneficial for sAML patients who typically have poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypomethylating Agents (HMAs) as Salvage Therapy in Relapsed or Refractory AML: An Italian Multicentric Retrospective Study. Lessi, F., Laurino, M., Papayannidis, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4728172/

Tolerability and Clinical Activity of Post-Transplantation ... Azacitidine is well tolerated in the majority of patients with acute myeloid leukemia after allogeneic stem cell transplantation. •. Administration of post- ...

2. nature.com nature.com/articles/s41598-025-98059-z

Maintenance therapy with Azacitidine for patients ... Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML).

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)32254-9/fulltext

Feasibility of allogeneic stem-cell transplantation after ... After a median of four cycles (range 1–11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1050/530512/Updated-Results-from-a-Phase-Clinical-Trial-Safety

Updated Results from a Phase Ⅱ Clinical Trial：Safety and ... Our results indicate that the combination of chidamide and azacitidine as a maintenance therapy for high-risk AML patients post allo-HSCT exhibits promising ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118630824

Acute Myeloid Leukemia (AML) Treated with Azacitidine ... Median survival of the 'funded' group was 12.2 months while median survival of the 'unfunded' group was 5.6 months (95% CI 3.3-7.7; p=0.0058). Of the AML ...

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

Real-world treatment patterns and outcomes with oral ... This study describes baseline and clinical characteristics, treatment patterns, survival, and safety outcomes of patients with acute myeloid leukemia (AML)

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04161885

NCT04161885 | A Study Evaluating Safety and Efficacy of ... The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid ...