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

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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug 5-Azacytidine for treating graft-versus-host disease?

Research shows that 5-Azacytidine can be effective in treating chronic graft-versus-host disease (cGvHD) in patients who do not respond to steroids, with some patients experiencing improved symptoms and quality of life. Additionally, it has been shown to prevent experimental graft-versus-host disease in animal models without affecting the beneficial graft-versus-leukemia effects. ^{1 2 3 4 5}

Is 5-Azacytidine safe for treating 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 the treatment well. In a study, 13 out of 14 patients tolerated the drug, and it showed promising results in improving symptoms and quality of life. ^{1 2 3 6 7}

How is the drug 5-Azacytidine unique in treating graft-versus-host disease?

5-Azacytidine is unique because it not only helps prevent graft-versus-host disease by increasing regulatory T cells (which help control the immune response) but also maintains the beneficial graft-versus-leukemia effects, making it a promising option for patients who do not respond well to standard steroid treatments. ^{1 2 3 8 9}

What is the purpose of this trial?

This study aims to evaluate the safety and feasibility of administering AZA in conjunction with steroids as first line therapy for GI GVHD. A risk for patients who have received a transplant from another donor is graft versus host disease (GVHD). This happens because of differences between the donated cells (graft) and the patient body's cells (host). The new cells from the donor might see the patients body's cells as different and attack them. GVHD can be very serious and cause death. The standard first treatment for GVHD is corticosteroids but not all patients respond and they then have to receive other treatments. In addition, when GHVD involves the gut it can damage stem cells and can cause long term gut problems such as abdominal pain bowel disturbance. In laboratory studies giving a medicine called 5 -azacytidine (AZA) has been able to protect the gut stem cells and help them recover. In this trial the investigators would like to see if AZA can do the same thing when given with steroids in patients with GVHD. Right now, doctors and researchers don't know the best treatment for GVHD. Acute GVHD is usually treated using high-dose corticosteroids, but these don't always work well. Even if the GVHD gets better when it involves the gut there can be long term damage to gut stem cells. In the laboratory 5 azacytidine (AZA) has been able to protect gut stem cells and help them recover and the investigators would like to learn if this happens in people too. AZA has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with leukemias. It has also been used post transplant to try and risk the chance of leukemia coming back and to try and treat GVHD but AZA has not been approved by the FDA for the treatment of acute GVHD.

Research Team

Helen Heslop, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

Known or suspected hypersensitivity to azacytidine

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

I am on dialysis.

Timeline

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

Treatment Details

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.

Participant Groups

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+

References

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

Azacitidine for the treatment of steroid-refractory chronic graft-versus-host disease: the results of the phase II AZTEC clinical trial. [2022]

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

Azacytidine prevents experimental xenogeneic graft-versus-host disease without abrogating graft-versus-leukemia effects. [2021]

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

Phase I-II Trial of Early Azacitidine after Matched Unrelated Donor Hematopoietic Cell Transplantation. [2023]

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

Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo. [2018]

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

5-azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. [2021]

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

Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibitory effects of 5-azapyrimidine nucleosides on cellular immunity. [2018]

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

Modulation of allogeneic CD8+ T-cell response by DZNep controls GVHD while preserving hematopoietic chimerism. [2021]