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

Trial Summary

What is the purpose of this trial?

Previous studies provide a rationale for administration of AZA after allo SCT for decreasing chimerism. The investigators hypothesize that azacitidine can be well tolerated after SCT and help decrease rate of decreasing donor chimerism and hence decrease relapse without increasing GVHD

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.

What data supports the effectiveness of the drug Azacitidine for treating myeloid leukemia after stem cell transplant?

Azacitidine has been shown to be effective in treating higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), including in patients who are not eligible for stem cell transplants. It has been proven to prolong overall survival compared to conventional care regimens, making it a recommended first-line treatment for these conditions. ^{1 2 3 4 5}

Is azacitidine safe for humans?

Azacitidine has been used safely in many patients with blood disorders like myelodysplastic syndromes and acute myeloid leukemia. Common side effects include low blood cell counts, fatigue, and fever, but serious side effects leading to stopping treatment are rare. ^{1 2 5 6 7}

How is the drug azacitidine unique for treating myeloid leukemia after stem cell transplant?

Azacitidine is unique because it is a hypomethylating agent that has been shown to prolong overall survival in patients with higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), compared to conventional care. It is administered subcutaneously (under the skin) and is the only approved drug in its class for these conditions, making it a valuable first-line treatment option. ^{1 2 3 5 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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 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 (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]

References

1. England pubmed.ncbi.nlm.nih.gov

Azacitidine access program for Belgian patients with myelodysplastic syndromes, acute myeloid leukemia or chronic myelomonocytic leukemia. [2018]

2. 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]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hypomethylating Agents (HMAs) as Salvage Therapy in Relapsed or Refractory AML: An Italian Multicentric Retrospective Study. [2021]

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

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

6. 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]

7. Switzerland 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. [2022]

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

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