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

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 2, single-arm, open-label study aims to evaluate the safety and efficacy of low-dose (25 mg/kg) post-transplant cyclophosphamide (PTCy) for prophylaxis of Graft-versus-Host Disease (GVHD) in patients undergoing allogeneic stem cell transplantation following reduced-intensity or non-myeloablative conditioning. The study will focus on matched sibling, matched unrelated, and haploidentical peripheral blood stem cell donors. The primary endpoint is 1-year GVHD-Free Relapse-Free Survival (GRFS). The study seeks to determine if low-dose PTCy offers similar outcomes as higher doses, with potentially reduced toxicity.

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.

What data supports the effectiveness of the drug Cyclophosphamide for preventing GVHD?

Research shows that Cyclophosphamide, when used after stem cell transplants, can effectively reduce the risk of graft-versus-host disease (GVHD), especially in cases involving matched donors. Studies have found that it lowers the incidence of both acute and chronic GVHD, helping patients avoid severe complications. ^{1 2 3 4 5}

Is cyclophosphamide safe for preventing GVHD in humans?

Cyclophosphamide has been used safely in humans to prevent graft-versus-host disease (GVHD) after stem cell transplants, with studies showing it can reduce GVHD rates without severe side effects. It is generally well-tolerated, with low rates of chronic GVHD and nonrelapse mortality, making it a promising option for GVHD prevention. ^{1 2 3 6 7}

How is the drug cyclophosphamide unique in preventing GVHD?

Cyclophosphamide is unique in preventing graft-versus-host disease (GVHD) because it can be used after transplantation to reduce GVHD without the need for T cell depletion, and it has a low incidence of chronic GVHD. It is administered in high doses shortly after transplantation, which is different from many other treatments that require long-term use. ^{1 3 5 7 8}

Research Team

Joseph Cioccio, MD

Principal Investigator

Penn State Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Post-transplant high-dose cyclophosphamide for the prevention of graft-versus-host disease. [2015]

2. United States 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. [2018]

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

The Use of Post-transplantation Cyclophosphamide in Peripheral Blood HLA-matched Stem Cell Transplantation as Graft-versus-host Disease Prophylaxis in Patients With Malignant or Non-malignant Hematologic Disorders: A Single-center Experience of 52 Patients. [2021]

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

Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. [2022]

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

Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease. [2015]

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

High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. [2021]

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

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. [2020]