PTCY + uhCG/EGF for Graft-versus-Host Disease Prophylaxis

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Henry Ford Health System

Disqualifiers: HIV, Hepatitis, Heart failure, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

So this a Phase I study with primary objective to determine the feasibility and safety of combining post-transplant cyclophosphamide and urinary-derived human chorionic gonadotropin and epidermal growth factor (uhCG/EGF) as graft versus host disease prophylaxis in stem cell transplant with MMUDs Secondary objectives are to determine the incidence acute and chronic GVHD, progression-free survival , and overall survival

Will I have to stop taking my current medications?

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 treatment PTCY + uhCG/EGF for preventing graft-versus-host disease?

Research shows that post-transplant cyclophosphamide (PTCy) is effective in reducing the incidence of severe acute graft-versus-host disease (GVHD) and improving survival outcomes in patients undergoing hematopoietic cell transplantation. Combining PTCy with other agents like anti-thymocyte globulin (ATG) has been shown to further reduce the risk of GVHD without increasing infection or relapse risks. ^{1 2 3 4 5}

Is the combination of PTCY and uhCG/EGF safe for humans?

The combination of post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) has been shown to be a safe approach for preventing graft-versus-host disease in patients undergoing stem cell transplants, with no increased risk of infection or relapse. ^{1 2 4 6 7}

How is the treatment PTCY + uhCG/EGF for graft-versus-host disease different from other treatments?

The treatment PTCY + uhCG/EGF is unique because it combines post-transplant cyclophosphamide (PTCY) with a novel component, uhCG/EGF (Pregnyl), which is not typically used in standard graft-versus-host disease (GvHD) prophylaxis. This combination may offer a new approach by potentially enhancing the effectiveness of PTCY in preventing GvHD, although specific details about the role of uhCG/EGF in this context are not well-documented in the available research. ^{1 2 4 6 8}

Research Team

Eligibility Criteria

This trial is for adults aged 18-70 with certain blood cancers needing a stem cell transplant but without matched donors. They must be mostly healthy, with good organ function and performance status. Women of childbearing age need a negative pregnancy test and must use birth control during the study.

Inclusion Criteria

My liver function tests are within normal limits and I don't have chronic hepatitis or cirrhosis.

Creatinine clearance should be >60 ml/min

I have a blood cancer and am eligible for a stem cell transplant without a full match.

Exclusion Criteria

I have a history of blood clots, a family history of it, am severely obese, or have thrombophilia.

My heart's pumping ability is weak, or I have a history of heart failure or heart disease.

I have had uterine fibroids in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

PTCY for 2 doses on day +3 and +4 after stem cell transplant followed by uhCG/EGF subcutaneously on day +7, +9 and +11 post stem cell transplant

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of acute and chronic GVHD

1 year

Treatment Details

Interventions

• uhCG/EGF (Graft Versus Host Disease Prophylaxis)

Trial Overview The study tests combining post-transplant cyclophosphamide (PTCY) with uhCG/EGF to prevent graft versus host disease after stem cell transplants from mismatched unrelated donors (MMUDs). It aims to assess safety, feasibility, and effects on disease progression and survival rates.

Participant Groups

Group I: PTCY and uhCG/EGF Experimental Treatment 1 Intervention

PTCY for 2 doses on day +3 and +4 after stem cell transplant followed by uhCG/EGF subcutaneously on day +7, +9 and +11 post stem cell transplant

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Findings from Research

In a study of 339 patients who received matched-unrelated donor hematopoietic cell transplantation, both anti-T-lymphocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) were found to have similar overall clinical outcomes in preventing graft-versus-host disease (GVHD).

However, the study revealed distinct patterns in T cell reconstitution: PTCy patients had higher levels of regulatory T cells, while ATG patients had higher levels of γδ T or NKT cells, indicating that different T cell populations may play a role in GVHD protection and could help tailor post-transplant care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy. Leserer, S., Graf, T., Franke, M., et al.[2023]

Combining post-transplant cyclophosphamide (PT-Cy) with rabbit anti-thymocyte globulin (ATG) has shown promise in reducing the incidence of chronic graft-versus-host disease (GvHD) without increasing infection or relapse risks in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Retrospective studies indicate that this combination therapy not only lowers the risk of acute and chronic GvHD but also improves overall survival rates, particularly GvHD-free, relapse-free survival (GRFS), compared to using ATG alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies. Duléry, R., Brissot, E., Mohty, M.[2023]

In a study involving 203 patients undergoing haemopoietic cell transplantation, pretreatment with anti-thymocyte globulin (ATG) significantly increased the likelihood of being free from long-term immunosuppressive treatment after 12 months, with 37% of the ATG group achieving this compared to only 16% in the control group.

While ATG treatment was associated with a higher incidence of Epstein-Barr virus reactivation, the overall safety profile was acceptable, as serious adverse events were similar between the ATG and control groups, indicating that ATG can be safely integrated into transplant regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Walker, I., Panzarella, T., Couban, S., et al.[2017]

In a study of 102 patients undergoing unrelated peripheral blood stem cell transplants (PBSCTs) for high-risk hematological malignancies, the combination of rabbit ATG and PTCy for graft-versus-host disease (GVHD) prophylaxis resulted in low rates of severe acute GVHD (11.8% in matched donors and 3.8% in mismatched donors).

The one-year overall survival rates were 75% for matched unrelated donor (MUD) transplants and 50% for mismatched unrelated donor (MMUD) transplants, indicating that the combination therapy is effective, especially in MUD cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants. Prem, S., Atenafu, EG., Al-Shaibani, Z., et al.[2019]

In a matched-pair analysis of 93 patients receiving posttransplant cyclophosphamide (PTCY) versus 179 patients receiving anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis in mismatched unrelated donor transplants, PTCY showed a significantly lower incidence of severe acute GVHD.

Patients treated with PTCY also experienced better outcomes in terms of leukemia-free survival and GVHD/relapse-free survival, suggesting that PTCY may be a more effective option for long-term disease control compared to ATG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Battipaglia, G., Labopin, M., Kröger, N., et al.[2021]

The low-dose anti-thymocyte (ATG) and low-dose post-transplant cyclophosphamide (PTCy) regimen effectively reduced the incidence of acute graft-versus-host disease (GVHD) in a study of 260 patients, with only 13.46% experiencing grade II-IV aGVHD by 180 days.

Long-term outcomes showed a 2-year overall survival rate of 60.7% and a relapse-free survival rate of 58.1%, indicating that this regimen not only prevents GVHD but also supports overall patient survival after haploidentical stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study. Li, X., Yang, J., Cai, Y., et al.[2023]

In a meta-analysis of 10 studies involving 1871 patients, post-transplant cyclophosphamide (PTCy) significantly reduced the incidence of acute graft-versus-host disease (aGVHD) and non-relapse mortality (NRM) compared to antithymocyte globulin (ATG).

PTCy also demonstrated improved overall survival (OS) and progression-free survival (PFS) without increasing the risk of relapse, suggesting it may be a more effective prophylactic option in allogeneic hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-transplant cyclophosphamide versus antithymocyte globulin in allogeneic hematopoietic cell transplantation: a meta-analysis. Gao, F., Zhang, J., Hu, J., et al.[2021]

In a study of 239 patients undergoing haploidentical hematopoietic cell transplant, the combination of low-dose post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) significantly reduced the incidence of severe acute graft-versus-host disease (GVHD) and non-relapse mortality compared to the standard ATG regimen.

The ATG/PTCy treatment improved GVHD-free, relapse-free survival rates, indicating its efficacy in preventing complications associated with transplant, although it was associated with slower recovery of blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. Wang, Y., Wu, DP., Liu, QF., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants. [2019]

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

Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Post-transplant cyclophosphamide versus antithymocyte globulin in allogeneic hematopoietic cell transplantation: a meta-analysis. [2021]

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

Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. [2023]