Using anti-T-lymphocyte immunoglobulin and cyclophosphamide to prevent graft-versus-host disease after stem cell transplantation

A Phase II Study of Neovii Anti-human T-lymphocyte Immunoglobulin (ATLG, Grafalon®) With Post Transplant Escalated Doses of Post-transplant-Cyclophosphamide to Prevent Acute and Chronic GVHD Post Allogeneic Stem Cell Transplantation

This study is testing if a combination of two treatments can help prevent graft-versus-host disease in patients with myelodysplastic syndromes or acute myeloid leukemia who are getting stem cell transplants from unrelated donors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sheba Medical Center (Government)
• Drugs / interventions: fludarabine
• Locations: 1 site (Ramat Gan)
• Trial ID: NCT03357159 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining anti-T-lymphocyte immunoglobulin (ATLG) with post-transplant cyclophosphamide (PTCy) in patients undergoing hematopoietic stem cell transplantation. The goal is to reduce the incidence of acute and chronic graft-versus-host disease (GVHD) while potentially shortening the duration of post-transplant immunosuppression. Eligible participants include those with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who are receiving matched unrelated donor transplants. The study aims to evaluate the safety and efficacy of this combination therapy in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with MDS or AML who are undergoing matched unrelated hematopoietic stem cell transplantation.

Not a fit: Patients with conditions other than AML or MDS, or those undergoing different types of transplantation, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of GVHD and improve recovery times for patients undergoing stem cell transplantation.

How similar studies have performed: Other studies have shown promising results with similar approaches in reducing GVHD, indicating that this methodology has potential based on prior findings.

Eligibility criteria

Inclusion Criteria:

1. Patients with MDS/AML
2. 18 years or older and willing and able to comply with the protocol requirements.
3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
5. Patients conditioned with reduced intensity or reduced toxicity conditioning of fludarabine with reduced dose (2 days) or myeloabalative doses (4 days) of busulfan or with treosulfan.
6. Patients must sign written informed consent.
7. Adequate birth control in fertile patients.

Exclusion Criteria:

1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
2. Patients with respiratory failure (DLCO \< 30%).
3. Active congestive heart failure (New York Heart Association \[NYHA\] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
4. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
5. Bilirubin \> 3.0 mg/dl, transaminases \> 3 times upper normal limit
6. Creatinine \> 2.0 mg/dl
7. ECOG-Performance status \> 2
8. Uncontrolled infection
9. Pregnancy or lactation
10. CNS disease involvement
11. Pleural effusion or ascites \> 1 liter.

Where this trial is running

Ramat Gan

• Chaim Sheba Medical Center — Ramat Gan, Israel (Recruiting)

Study contacts

• Principal investigator: Arnon Nagler, MD — Sheba Medical Center
• Study coordinator: Arnon Nagler, MD

Conditions Graft Versus Host Disease; anti thymocyte globulin; cyclophospamide; graft-versus-host disease; stem cell transplantation