Cyclophosphamide for Graft-versus-Host Disease

(PTCYGVHD Trial)

Overseen By IIT OFFICE

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Nebraska

Disqualifiers: Previous transplants, Liver disease, Myelofibrosis, 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

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different doses of cyclophosphamide, a chemotherapy medication, can improve life after a stem cell transplant for individuals with certain blood disorders. Researchers aim to determine if a lower dose of the drug can reduce the risks of graft-versus-host disease (GVHD), a common complication post-transplant. Participants will receive either the standard high dose or an experimental lower dose, along with other medications to prevent GVHD. Adults aged 60 or older with a serious blood condition and an available donor match may be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using cyclophosphamide after a stem cell transplant can help prevent graft-versus-host disease (GVHD), where new stem cells attack the body. Both high and low doses of cyclophosphamide have been studied.

One study found that low-dose cyclophosphamide effectively reduces GVHD, with patients tolerating this dose well and experiencing side effects similar to those with higher doses. Another study showed that using cyclophosphamide after a transplant resulted in good survival rates one year later, with a low risk of the new stem cells not functioning properly, which is encouraging.

Overall, both doses of cyclophosphamide appear well-tolerated. While there are some risks of side effects, these are similar regardless of dose, suggesting the treatment is generally safe for humans. However, it is important to discuss any concerns with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they are exploring different doses of cyclophosphamide to improve outcomes for graft-versus-host disease (GVHD) after stem cell transplantation. Unlike the standard high-dose regimen, which is already part of the care protocol and includes doses of 50 mg/kg, the attenuated-dose approach uses a lower dose of 25 mg/kg. This lower dose might reduce side effects while still effectively preventing GVHD. The goal is to find a balance between efficacy and tolerability, potentially offering a gentler option for patients without compromising the protective effects against GVHD.

What evidence suggests that this trial's treatments could be effective for graft-versus-host disease?

In this trial, participants will receive either high-dose or attenuated-dose cyclophosphamide as part of their treatment regimen. Research has shown that both low and high doses of cyclophosphamide can help prevent graft-versus-host disease (GVHD), a condition where transplanted cells attack the body. Studies indicate that using a lower dose of cyclophosphamide after a transplant can reduce GVHD as effectively as higher doses. This approach may result in fewer side effects for patients while maintaining the same level of protection. Additionally, cyclophosphamide has effectively controlled GVHD in various types of transplants. These findings suggest that cyclophosphamide, whether in low or high doses, effectively manages GVHD. ^{1 6 7 8 9}

Who Is on the Research Team?

Moataz Ellithi, MBChB

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for individuals who have received an allogeneic hematopoietic stem cell transplant to treat various blood cancers and are at risk of developing graft-versus-host disease (GVHD). Specific eligibility criteria details were not provided.

Inclusion Criteria

I need a bone marrow transplant for my blood cancer or disorder.

I am scheduled for a stem cell transplant with a matching donor.

I am mostly independent and can care for myself.

Exclusion Criteria

I will receive high doses of cyclophosphamide before my stem cell transplant.

I have been diagnosed with myelofibrosis.

My heart's pumping ability is reduced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation and Initial Treatment

Participants receive allogeneic hematopoietic stem cell transplantation followed by high-dose or attenuated-dose cyclophosphamide and GVHD prophylaxis

4 weeks

In-patient stay for transplantation and initial treatment

Post-Transplant Monitoring

Participants are monitored for health-related quality of life, functional outcomes, GVHD, relapse, survival, and toxicities

3 months

Regular follow-up visits

Follow-up

Participants are monitored for long-term outcomes including overall survival, event-free survival, and incidence of GVHD

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Attenuated-dose Cyclophosphamide
• High-dose Cyclophosphamide
• Mycophenolate Mofetil (MMF)
• Sirolimus

Trial Overview

The study compares the effects of standard versus reduced doses of post-transplant cyclophosphamide, along with a two-drug regimen for preventing GVHD, which includes Mycophenolate Mofetil (MMF) and Sirolimus.

How Is the Trial Designed?

Group I: Attenuated-dose post-transplant cyclophosphamide (PTCy) Arm Experimental Treatment 3 Interventions

Participants will receive attenuated-dose post-transplant cyclophosphamide (PTCy) at 25 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.

Group II: High-dose post-transplant cyclophosphamide (PTCy) Arm: Standard of Care Active Control 3 Interventions

Participants will receive high-dose post-transplant cyclophosphamide (PTCy) at 50 mg/kg on days +3 and +4 after allogeneic hematopoietic stem cell transplantation. This is in addition to sirolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

In a study of 43 Fanconi anemia patients undergoing marrow transplantation with a reduced cyclophosphamide (CY) conditioning regimen (15 mg/kg/day for 4 days), 93% of patients are alive after a median follow-up of 3.7 years, indicating high efficacy and safety of this approach.

The study shows that using lower doses of CY results in low incidences of acute and chronic graft-versus-host disease (17% and 28.5%, respectively), confirming that this conditioning method minimizes toxicities while achieving successful engraftment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide. Bonfim, CM., de Medeiros, CR., Bitencourt, MA., et al.[2021]

In a murine model of MHC-haploidentical hematopoietic cell transplantation, administering post-transplantation cyclophosphamide (PTCy) on days +3/+4 was found to be the most effective timing for preventing graft-versus-host disease (GVHD), outperforming other dosing schedules.

The study revealed that both the timing and dosage of PTCy are crucial for its efficacy, with lower doses given on days +1/+2 leading to accelerated death, highlighting the importance of optimizing PTCy protocols in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized Timing of Post-Transplantation Cyclophosphamide in MHC-Haploidentical Murine Hematopoietic Cell Transplantation. Wachsmuth, LP., Patterson, MT., Eckhaus, MA., et al.[2021]

High-dose posttransplantation cyclophosphamide, when combined with tacrolimus and mycophenolate mofetil, has been shown to effectively prevent graft-versus-host disease (GvHD) in patients receiving allogeneic blood or marrow transplants, even with HLA-mismatched donors.

This treatment strategy takes advantage of the drug's ability to target proliferating alloreactive T cells while sparing nonalloreactive T cells, making it a promising option for improving GvHD prophylaxis and expanding donor options for patients, including those with conditions like sickle cell anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cyclophosphamide for graft-versus-host disease prevention. Luznik, L., Jones, RJ., Fuchs, EJ.[2021]

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.

portlandpress.com

portlandpress.com/clinsci/article/139/21/CS20257272/236665/Low-and-high-dose-post-transplant-cyclophosphamide

Low- and high-dose post-transplant cyclophosphamide ...

This study aimed to determine whether lower doses of PTCy can reduce GVHD and to examine the effects of PTCy doses on human (h) immune cell ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41151059/

Low- and high-dose post-transplant cyclophosphamide ...

This study indicates that low-dose PTCy reduces GVHD with similar efficacy to that of high-dose PTCy, but this appears to be associated with ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.24.00184

Post-Transplant Cyclophosphamide–Based Graft-Versus- ...

We evaluated whether post-transplant cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA- ...

4.

jitc.bmj.com

jitc.bmj.com/content/9/2/e001818

Post-transplantation cyclophosphamide reduces the ...

Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2–4 acute GVHD compared ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10141544/

Characteristics of Graft-versus-Host Disease (GvHD) after Post ...

Post--transplantation cyclophosphamide (PTCy) has been shown to effectively control GvHD in haploidentical (Haplo) transplants.

6.

ascopubs.org

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

Post-Transplant Cyclophosphamide-Based Graft-Versus ...

PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless ...

7.

nature.com

nature.com/articles/s41598-025-07263-4

A comparative study of GVHD prophylaxis using low dose ...

The probabilities of overall and progression-free survival were 83.4% and 70.0% in the ATG group and 76.5% and 75.2% in the PTCy group, ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636724002914

Graft Failure Incidence, Risk Factors, and Outcomes in ...

The incidences of primary and secondary graft failure in patients receiving non-myeloablative alloHCT with PTCy-based GVHD prophylaxis are low.

9.

frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1225748/full

Graft-versus-host disease: teaching old drugs new tricks at ...

After 18 months of follow-up, 18% of patients had grade III–IV aGVHD at 100 days. Moderate-to-severe cGVHD at 1 year was 3%, with GVHD-free, relapse-free ...