Cyclophosphamide for GVHD Prevention

(GVHD-PTCy Trial)

Overseen By Joseph Cioccio, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Milton S. Hershey Medical Center

Must not be taking: Investigational agents, Immunosuppressants

Disqualifiers: Prior transplant, CNS involvement, Infections, HIV, Heart issues, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a low dose of cyclophosphamide to determine if it can safely prevent Graft-versus-Host Disease (GVHD) in individuals undergoing a stem cell transplant. GVHD occurs when new stem cells attack the body. The trial targets individuals with specific types of leukemia or lymphoma who plan to receive a transplant from a related or unrelated donor. Suitable candidates for this trial are those needing a stem cell transplant for these conditions and having a potential donor. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on steroids at a dose higher than 10 mg/day, you may not be eligible to participate.

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

Research has shown that post-transplant cyclophosphamide (PTCy) is generally well-tolerated for preventing graft-versus-host disease (GVHD) after stem cell transplants. GVHD occurs when donor cells attack the patient's body, and studies have found that cyclophosphamide can help reduce this risk.

One study found that using a low dose of PTCy with alemtuzumab was linked to low relapse rates and fewer cases of both sudden and long-term GVHD. It also showed that serious side effects were uncommon.

Overall, evidence suggests that low-dose cyclophosphamide is a promising option with manageable risks for people undergoing stem cell transplants, making it a potential choice for those concerned about GVHD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for graft-versus-host disease (GVHD) that often involve higher doses or different combinations of immunosuppressants, this approach uses a low-dose of cyclophosphamide after a stem cell transplant. Researchers are excited about this treatment because it potentially reduces the risk of GVHD while preserving the benefits of the transplant. By combining low-dose cyclophosphamide with tacrolimus and mycophenolate mofetil, this method aims to strike a balance between effective GVHD prevention and minimizing side effects, offering hope for improved patient outcomes.

What evidence suggests that low-dose cyclophosphamide is effective for GVHD prevention?

This trial will evaluate the use of low-dose cyclophosphamide (PTCy) for preventing graft-versus-host disease (GVHD). Studies have shown that administering a low dose of cyclophosphamide after a transplant can help prevent GVHD, a condition where the donor's cells attack the patient's body. Research indicates that using low-dose PTCy after stem cell transplants from matched donors can reduce both sudden and long-term GVHD compared to other treatments. In previous studies, about 78.6% of patients who received less intense or non-aggressive treatment before their transplant survived for at least one year. This suggests that low-dose PTCy effectively prevents GVHD and may have fewer side effects than higher doses. ^{1 5 6 7 8}

Who Is on the Research Team?

Joseph Cioccio, MD

Principal Investigator

Penn State Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with blood cancers or uterine tumors who are undergoing a stem cell transplant. It's open to those receiving cells from siblings, unrelated matches, or half-matched donors after less intense conditioning. People can't join if they don't meet specific health criteria set by the researchers.

Inclusion Criteria

Pulmonary function: must have FEV1 of at least 50% predicted, and DLCO corrected for hemoglobin of at least 40% predicted

I have leukemia with low levels of cancer cells in my blood and bone marrow.

I have MDS or CMML with low levels of immature blood cells.

Exclusion Criteria

Use of investigational agents

Seropositive for human immunodeficiency virus (HIV) with detectable viral load, hepatitis B virus (HBV) or hepatitis C virus (HCV) with detectable viral load. Hepatitis B surface antibody positive due to vaccination or natural immunity are permitted. Patients previously treated for HCV and considered to be in sustained virologic remission (SVR) are allowed

Pregnant or lactating female patients (unless feeding via formula). Women of childbearing potential (WOCBP) are required to have a negative serum or urine pregnancy test prior to conditioning regimen

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo reduced-intensity or non-myeloablative conditioning prior to transplantation

1-2 weeks

Transplantation

Participants receive allogeneic hematopoietic stem cell transplantation

1 week

Inpatient stay for transplantation

Treatment

Participants receive low-dose post-transplant cyclophosphamide (PTCy) on days +3 and +4, in combination with tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on 1-year GVHD-Free Relapse-Free Survival (GRFS)

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide

Trial Overview The study tests whether a low dose of Cyclophosphamide after transplant can prevent GVHD without causing too much harm. All participants will receive this treatment following their stem cell transplant and will be monitored for one year to see how well it works and how safe it is.

How Is the Trial Designed?

Group I: Low-Dose PTCy for GVHD Prophylaxis Experimental Treatment 1 Intervention

Participants in this single-arm study will receive low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) on days +3 and +4 following allogeneic hematopoietic stem cell transplantation. This will be administered in combination with tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. The study includes patients receiving transplants from matched sibling, matched unrelated, single allelic mismatched unrelated, and haploidentical donors following reduced-intensity or non-myeloablative conditioning.

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Published Research Related to This Trial

In a study of 35 patients undergoing allogeneic peripheral blood stem cell transplantation (alloPBSCT), a combination of post-transplant cyclophosphamide and standard immunosuppressants effectively reduced the incidence of acute and chronic graft-versus-host disease (GVHD) to 17% and 7%, respectively, with no severe grade IV GVHD cases reported.

The approach resulted in an impressive 2-year nonrelapse mortality rate of just 3% and maintained overall survival at 77%, demonstrating that this strategy not only controls GVHD but also preserves the beneficial graft-versus-tumor effect essential for combating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. Carnevale-Schianca, F., Caravelli, D., Gallo, S., et al.[2018]

High-dose cyclophosphamide used as a single-agent prophylaxis after myeloablative allogeneic bone marrow transplantation significantly reduced the incidence of acute graft-versus-host disease (GVHD), with rates of 43% for grades II-IV and 10% for grades III-IV among 117 patients.

The treatment also demonstrated promising long-term outcomes, with a 2-year overall survival rate of 55% and a low cumulative incidence of chronic GVHD at 10%, indicating its efficacy and safety in patients with advanced hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Luznik, L., Bolaños-Meade, J., Zahurak, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31481121/

Low-dose post-transplant cyclophosphamide and anti ... Conclusions: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503189

Graft-versus-Host Disease Prophylaxis with ... Data from two randomized trials have suggested that post-transplantation cyclophosphamide can reduce the risk of GVHD after SCT from a matched ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00856

Post-Transplant Cyclophosphamide-Based Graft-Versus ... The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1569149/full

Low-dose ATG/PTCy for graft-versus-host disease ... The 2-year overall survival, disease-free survival, non-relapse mortality and CI of relapse were 66.7%, 54.8%, 25.5% and 19.7%, respectively. Between 7.5 and 5 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0952791525001384

Post-transplant cyclophosphamide for graft-versus-host ... While data suggest lower doses can hasten engraftment and reduce viral infections without compromising GVHD control, the ultimate impact on the graft-versus ...

6. link.springer.com link.springer.com/article/10.1007/s00277-025-06657-8

Safety and feasibility of intermediate-dose post-transplant ... Safety and feasibility of intermediate-dose post-transplant cyclophosphamide for graft-versus-host disease prophylaxis. Case Report; Open ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10558021/

Post-Transplant Cyclophosphamide for the Prevention of ... Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical ...

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2155/529226/Low-Dose-Post-Transplant-Cyclophosphamide-in

Low Dose Post-Transplant Cyclophosphamide in ... Our data suggest that low dose PTCy in combination with alemtuzumab is associated with low relapse rates and acute and chronic GvHD, with a safe side effect ...