Cyclophosphamide for Graft-versus-Host Disease

(PTCYGVHD Trial)

Overseen By Vijaya R Bhatt, MBBS

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

Trial Summary

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.

What data supports the effectiveness of the drug Cyclophosphamide for Graft-versus-Host Disease?

Research shows that high-dose cyclophosphamide can effectively prevent graft-versus-host disease (GVHD) after bone marrow transplantation, with a study reporting a 10% incidence of severe GVHD and a 55% overall survival rate at two years. However, its effectiveness as a sole treatment in certain transplant settings may be limited, as another study found a high rate of severe GVHD when used alone in a different type of transplant. ^{1 2 3 4 5}

Is cyclophosphamide safe for use in humans?

Cyclophosphamide has been used in various doses for preventing graft-versus-host disease (GVHD) in bone marrow transplants, showing generally low toxicity and good survival rates in some studies. However, high doses can lead to severe acute GVHD in certain settings, and reducing the dose may improve safety and recovery in elderly patients. ^{2 3 6 7 8}

How does the drug cyclophosphamide work for graft-versus-host disease?

Cyclophosphamide is unique for graft-versus-host disease because it is used in high doses after transplantation to prevent both graft rejection and the disease itself by suppressing the immune response. This approach is different from other treatments as it leverages cyclophosphamide's ability to spare early stem cells while targeting immune cells, making it a potent yet non-damaging option. ^{1 2 5 9 10}

What is the purpose of this trial?

This study will compare post-transplant health-related quality of life following the use of standard versus attenuated dose of post-transplant cyclophosphamide in addition to two-drug graft-versus-host disease (GVHD) prophylaxis among recipients of allogeneic hematopoietic stem cell transplant.

Research Team

Vijaya R Bhatt, MBBS

Principal Investigator

University of Nebraska

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

High-dose cyclophosphamide for graft-versus-host disease prevention. [2021]

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

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

3. 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]

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

Optimized Timing of Post-Transplantation Cyclophosphamide in MHC-Haploidentical Murine Hematopoietic Cell Transplantation. [2021]

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

High-dose cyclophosphamide for aplastic anemia and autoimmunity. [2019]

6. United States 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. [2021]

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

HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. [2022]

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

Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies. [2023]

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

Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. [2019]

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

High dose cyclophosphamide treatment for autoimmune disorders. [2018]