5-Azacytidine With Steroids for Gastrointestinal GVHD (5-AZA FOR GVHD)

NCT06598332 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: H-55921 5-AZA for GVHD
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Graft-Versus-Host Disease(GVHD)

Keywords

Graft-Versus-Host-Disease; GVHD; 5-AZACYTIDINE

Outcome Measures

Primary Outcomes (2)

• Feasibility rate

  The proportion of patients who can tolerate and complete one cycle of AZA (5-day) in combination with steroid among patients who are eligible and receive at least one dose of AZA.

  30 days after first dose of AZA

• Treatment-related adverse event (tAE) rate

  The proportion of patients who develop any Grade 3-5 adverse events (per Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0) that are considered probably, or definitely related to AZA or AZA in combination with steroid that occur in the first cycle of combination therapy until 30 days after first dose of AZA.

  30 days after first dose of AZA

Secondary Outcomes (4)

• GVHD response rate

  Day 28

• Overall survival (OS)

  6 months and 12 months after combination therapy initiation

• Progression-free survival (PFS)

  6 months and 12 months after combination therapy initiation

• Systemic Infections

  30 days after last dose of AZA

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: 5-Azacytidine

Interventions

5-Azacytidine DRUG

Patients will be treated with 5 azacytidine at a dose of 32 mg/m2 SQ or IV. The investigators aim to start AZA on Day 1 of steroids but it can be started up to 72 hours after steroids are started . Patients will be premedicated with antiemetics. Patients must receive steroids at a minimum dose of prednisone 2 mg/kg/day PO (or methylprednisolone 1.6 mg/kg/day IV) divided into 1-2 daily doses as therapy for acute GVHD. For patients that weigh over 100 kg, maximal starting dose of prednisone will be 200 mg (or methylprednisolone-equivalent). Steroid Taper for responding patients (Prednisone/Methylprednisolone) Days 1-5 2 mg/kg/day (taper cannot start until 3 days after enrollment) Days 6-10 1.5 mg/kg/day Day 11-15 1.0 mg/kg/day Days 16-20 0.5 mg/kg/day Days 21-28\* 0.25 mg/kg/day Days 29-56 Gradual further taper with a goal of reaching \< 0.2 mg/kg/day of prednisone (or \< 0.16 mg/kg/day of methylprednisolone) by Day 56.

Treatment

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 12 years of age or older at time of enrollment.
• Patients experiencing their initial presentation of stage 1 or greater acute LGI GVHD requiring systemic therapy after allogeneic transplant for any malignant or non-malignant indication using any graft/donor source or conditioning intensity.
• 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.
• Patients should not have received systemic immune suppressive therapy for treatment of active GVHD except for a maximum of 72 hours of steroid therapy prior to enrollment. Topical skin and GI corticosteroids (such as budesonide and oral beclomethasone diproprionate) are allowed.
• Informed Consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

You may not qualify if:

• Relapsed, progressing or persistent malignancy or evidence of minimal residual disease (MRD) requiring withdrawal of systemic immune suppression.
• Patients with acute GVHD developing after administration of a donor lymphocyte infusion (DLI) for relapse / progression of disease. Patients with acute GVHD after planned donor lymphocyte infusion or planned T cell or NK cell add back are eligible.
• Patients with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms
• Patients receiving other drugs for the treatment of GVHD. Note, GVHD prophylaxis agents (e.g., calcineurin inhibitors) may be continued at local Investigator's discretion.
• Patients on renal replacement therapy.
• Patients requiring continuous supplemental oxygen (O2 requirement \>2L/min to maintain peripheral O2 saturation \[SpO2\] \>90%).
• Patients with active hepatic sinusoidal obstructive syndrome (SOS) and/or clinical evidence of impaired hepatic function (ascites or encephalopathy related to liver disease)
• Abnormal coagulation parameters (PT \> 15 seconds, PTT \> 40 seconds, and/or INR \>1.5)
• Significant active cardiac disease within the previous 6 months including:
• NYHA class 4 CHF Unstable angina Myocardial infarction
• Known or suspected hypersensitivity to azacytidine.
• Platelets \<20 and or absolute neutrophil count (ANC) \< 1000.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Helen Heslop, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: September 19, 2024
• Study Start: August 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: September 22, 2025

Record last verified: 2025-08

Locations

US (2)