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

Overseen By shatha farhan

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Henry Ford Health System

Disqualifiers: HIV, Hepatitis, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and feasibility of combining two treatments, post-transplant cyclophosphamide (PTCY) and urinary-derived human chorionic gonadotropin with epidermal growth factor (uhCG/EGF), to prevent graft-versus-host disease (GVHD) in stem cell transplant patients. GVHD occurs when donated stem cells attack the recipient's body. The trial targets individuals with blood cancers who need a stem cell transplant but lack a fully matched donor. Candidates should not have asthma or severe headaches and must be cancer-free for at least two months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research shows that adding uhCG/EGF to standard treatments could effectively manage severe cases of acute graft-versus-host disease (GVHD). In earlier studies, patients tolerated uhCG/EGF well, and it aided the healing process for GVHD. These results suggest that uhCG/EGF might be safe for people. However, this study is in its early stages and primarily focuses on assessing safety. While the treatment appears promising, more information is needed to fully understand its safety in this context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using uhCG/EGF for graft-versus-host disease prophylaxis because it introduces a novel approach to managing this condition. Unlike traditional treatments that often rely on immunosuppressive drugs, uhCG/EGF incorporates human chorionic gonadotropin and epidermal growth factor to potentially enhance tissue repair and reduce inflammation. This combination could offer a more targeted method of preventing graft-versus-host disease, potentially reducing the side effects associated with broader immunosuppression. Additionally, the subcutaneous delivery of uhCG/EGF at specific intervals post-transplantation is designed to optimize the timing of immune modulation, offering a strategic advantage over existing therapies.

What evidence suggests that this treatment might be an effective treatment for graft-versus-host disease?

Research has shown that uhCG/EGF, administered alongside PTCY in this trial, might reduce the severity of acute graft-versus-host disease (aGVHD), a serious condition following a stem cell transplant. One study found that 68% of patients responded positively to uhCG/EGF by day 28, with 57% achieving complete recovery. Another study reported that 62% of high-risk patients experienced complete recovery. This treatment is promising because it may also decrease the need for steroids, which often cause side effects. Overall, uhCG/EGF appears to be a promising therapy for managing aGVHD. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• uhCG/EGF

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.

How Is the Trial Designed?

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

uhCG/EGF is already approved in United States for the following indications:

Approved in United States as uhCG/EGF for:

• Acute graft-versus-host disease (GVHD)

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Published Research Related to This Trial

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]

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 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 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]

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 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]

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]

Citations

1. astctjournal.org astctjournal.org/article/S2666-6367(23)01323-4/fulltext

Phase II, Open-Label Clinical Trial of Urinary-Derived ... uhCG/EGF could reduce the morbidity and mortality of severe aGVHD; a steroid-sparing role is possible. ABSTRACT. Treatments that aid ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723013234

Phase II, Open-Label Clinical Trial of Urinary-Derived ... The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7160256/

Facilitating resolution of life-threatening acute GVHD with ... uhCG is a readily available and promising supportive therapy for life-threatening aGVHD. uhCG also contains EGF, which could aid in the repair ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37279855/

Phase II, Open-Label Clinical Trial of Urinary-Derived Human ... The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response).

5. gvhdhub.com gvhdhub.com/medical-information/uhcg-plus-egf-granted-orphan-drug-designation-for-the-treatment-of-acute-graft-versus-host-disease

uhCG plus EGF granted orphan drug designation for the ... In terms of efficacy, a complete response at Day 28 was observed in 62% of patients in the high-risk group and 54% of patients receiving second- ...

6. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/261/479562/Phase-2-Results-of-Urinary-Derived-Human-Chorionic

Phase 2 Results of Urinary-Derived Human Chorionic ... Conclusion: Our Phase 2 study demonstrates that uhCG/EGF is a promising addition to systemic therapy in patients with life-threatening aGVHD.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05123040

Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF ... This is a single arm study designed to determine the lowest dose of corticosteroids required (toxicity endpoint) without impairing GVHD complete response or ...