5-Azacytidine + Steroids for Graft-versus-Host Disease

No longer recruiting at 1 trial location

Overseen By Helen Heslop, MD

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: Baylor College of Medicine

Must be taking: Corticosteroids

Must not be taking: Other GVHD drugs

Disqualifiers: Relapsed malignancy, Uncontrolled infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating graft-versus-host disease (GVHD), which can occur after a transplant. Researchers aim to determine if adding the drug 5-azacytidine (AZA, also known as Vidaza or Onureg) to standard steroid treatment can better protect and heal the gut when GVHD affects it. The trial targets patients who have just begun experiencing GVHD in the gut and are starting steroid treatment. Participants should not have received other immune-suppressing treatments for GVHD, except for a short course of steroids. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic immune suppressive therapy for active GVHD, except for up to 72 hours of steroid therapy before joining the trial. You can continue using topical skin and GI corticosteroids.

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

Research has shown that 5-azacytidine (AZA) is generally safe for people. In previous studies, most patients tolerated it well, even when combined with steroids to treat chronic graft-versus-host disease (GVHD). The FDA has already approved AZA for some types of leukemia, supporting its safety profile. However, while AZA has been used in clinical settings for GVHD, it is not yet FDA-approved for this specific condition. This trial is in its early stages, and researchers are still gathering detailed safety information. So far, AZA appears to be well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for graft-versus-host disease (GVHD) that primarily involves steroids, 5-Azacytidine offers a fresh approach. This drug is unique because it works by modifying the DNA of immune cells, potentially reducing their attack on the body without suppressing the immune system as broadly as steroids do. Researchers are excited about 5-Azacytidine since it might provide a more targeted way to manage GVHD, potentially improving patient outcomes and offering relief more quickly than traditional treatments.

What evidence suggests that 5-Azacytidine combined with steroids might be an effective treatment for graft-versus-host disease?

Research has shown that 5-azacytidine (AZA), administered alongside standard steroid treatment in this trial, might protect gut stem cells from damage caused by graft-versus-host disease (GVHD). Lab studies have found that AZA aids the recovery of these crucial cells. Although AZA is not yet approved for treating GVHD, it has shown promise in preventing it in some experimental models without affecting the positive effects of transplants. AZA is already approved for treating certain types of leukemia, indicating that its safety is well understood. Early data also suggests that AZA could help manage GVHD, providing a reason for further research. ^{1 3 6 7 8}

Who Is on the Research Team?

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older who are experiencing their first episode of acute lower gastrointestinal GVHD after an allogeneic transplant. They must not have had more than 72 hours of steroid treatment for GVHD, except topical steroids. A biopsy is encouraged but not mandatory.

Inclusion Criteria

Patients can be enrolled with only a clinically established diagnosis. Biopsy of involved organs with acute GVHD is encouraged but is not required and should not delay study entry

I am 12 years old or older.

Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria

Platelets <20 and or absolute neutrophil count (ANC) < 1000

Known or suspected hypersensitivity to azacytidine

I am on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive one cycle of AZA with steroids for 5 days

1 week

Daily visits for 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits at 1, 2, 4, 8 weeks, and 3, 6, 12 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-Azacytidine

Trial Overview The study tests the safety and effectiveness of combining a drug called AZA with steroids as the initial treatment for GI GVHD. Researchers want to see if AZA can protect gut stem cells and aid recovery in patients suffering from this condition.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Patients will receive one cycle of AZA through the vein or as a shot under the skin daily for 5 days. This will start at the same time or within 3 days of starting standard treatment for gut GVHD with steroids.

5-Azacytidine is already approved in United States, European Union for the following indications:

Approved in United States as Vidaza for:

• Myelodysplastic syndromes (MDS)
• Acute myeloid leukemia (AML)

Approved in European Union as Vidaza for:

• Myelodysplastic syndromes (MDS)
• Acute myeloid leukemia (AML)
• Chronic myelomonocytic leukemia (CMML)

Approved in United States as Onureg for:

• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5467988/

Azacytidine prevents experimental xenogeneic graft-versus ... In summary, our data demonstrate that AZA prevents xGVHD without abrogating graft-vs.-leukemia effects. These findings could serve as basis for further studies ...

2. ashpublications.org ashpublications.org/bloodadvances/article/4/21/5580/474117/A-phase-3-randomized-study-of-5-azacitidine

A phase 3 randomized study of 5-azacitidine maintenance vs ... In this phase 3, open-label, randomized trial, azacitidine maintenance did not improve RFS after transplant in high-risk AML/MDS.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06598332

5-Azacytidine With Steroids for Gastrointestinal GVHD (5- ... This study aims to evaluate the safety and feasibility of administering AZA in conjunction with steroids as first line therapy for GI GVHD.

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02204020/

Clinical Trial: NCT02204020 Moreover, 5-aza has properties that suggest protection against graft-versus-host disease (GVHD) as well. Preliminary data shows that it is well ...

5. astctjournal.org astctjournal.org/article/S1083-8791(10)00446-5/pdf

5-Azacytidine as Salvage Treatment in Relapsed Myeloid ... Only 1 patient has died (of disease progression), and no flares of graft-versus-host disease (GVHD) were observed with 5-azacytidine. As of latest follow-up, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5541679/

Azacitidine mitigates GvHD via differential effects on the ... Azacitidine (AzaC) mitigates Graft vs. Host Disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723014744

Phase I-II Trial of Early Azacitidine after Matched Unrelated ... Graft-versus-host disease induced graft-versus-leukemia effect: greater impact on relapse and disease-free survival after reduced intensity conditioning.

8. withpower.com withpower.com/trial/early-phase-1-graft-versus-host-disease-cgvhd-9-2024-e0f18

5-Azacytidine + Steroids for Graft-versus-Host Disease Research shows that 5-Azacytidine, also known as Azacitidine, is generally safe for treating chronic graft-versus-host disease, with most patients tolerating ...