ATG + PTCy for Graft-versus-Host Disease Prophylaxis

Not currently recruiting at 10 trial locations

Overseen By Sarah Garisto, BSc

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: McMaster University

Must not be taking: T-cell antibody

Disqualifiers: HIV, Pregnancy, Infection, 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: 2

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments to determine their effectiveness in preventing chronic graft-versus-host disease, a condition that can occur after a stem cell transplant. One group receives anti-thymocyte globulin (a drug that suppresses the immune system) with cyclophosphamide (a chemotherapy drug), while the other group receives only anti-thymocyte globulin. It targets individuals with acute myeloid leukemia or myelodysplastic syndrome undergoing their first stem cell transplant. Participants should have a well-matched related or unrelated donor and no active infections. Meeting these criteria may make this trial a suitable option. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are taking T-cell antibody prophylaxis. It's best to discuss your specific medications with the trial team.

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

Research has shown that using anti-thymocyte globulin (ATG) with post-transplant cyclophosphamide (PTCy) is generally safe for patients. One study found that adding PTCy to ATG did not increase side effects in the first 100 days, suggesting the combination is well-tolerated in the short term.

ATG effectively lowers the risk of graft rejection and graft-versus-host disease (GvHD), a condition where transplanted cells attack the body. However, using ATG alone might increase the risk of infections.

Overall, combining ATG and PTCy seems to provide a balanced approach to reducing GvHD while maintaining patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Anti-Thymocyte Globulin (ATG) and Post-Transplant Cyclophosphamide (PTCy) for preventing Graft-versus-Host Disease (GVHD) because it introduces a novel approach to immune modulation. While traditional treatments often rely solely on immunosuppressants, this combination leverages PTCy’s unique ability to selectively eliminate alloreactive T cells post-transplant, potentially reducing the risk of GVHD without broadly suppressing the immune system. Moreover, by integrating cyclophosphamide shortly after transplantation, it targets early immune reactions more precisely, which could lead to better outcomes and fewer side effects compared to standard prophylaxis methods.

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

Studies have shown that combining anti-thymocyte globulin (ATG) with post-transplant cyclophosphamide (PTCy) effectively lowers the risk of graft-versus-host disease (GVHD), a condition where the donor's immune cells attack the recipient's body. In this trial, one group of participants will receive ATG and PTCy together. Research indicates that patients who received this combination had better survival rates without GVHD or cancer recurrence compared to those who did not receive PTCy. Specifically, one study found that 49% of patients remained free from GVHD and cancer relapse three years after receiving the combination treatment. These promising results suggest that ATG and PTCy together can be a strong option for preventing GVHD after a transplant. ^{2 3 4 6 7}

Who Is on the Research Team?

Irwin R Walker, MBBS

Principal Investigator

McMaster University

Kristjan Paulson, MD

Principal Investigator

CancerCare Manitoba

Are You a Good Fit for This Trial?

This trial is for individuals aged ≥16 with acute myeloid leukemia in remission or myelodysplastic syndrome, planning their first stem cell transplant from a fully matched donor. They must be medically fit, have good performance status, and agree to use contraception post-transplant. Exclusions include pregnancy, breastfeeding, HIV positivity, certain prior cancers or treatments.

Inclusion Criteria

I meet the criteria for a bone marrow transplant at my treatment center.

This is my first time receiving a transplant.

Ability and willingness to comply with study procedures and schedule, in the Investigator's opinion

Exclusion Criteria

I have difficulty urinating due to a blockage.

I am preparing for my second transplant.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive Anti-Thymocyte Globulin (ATG) with or without Post Transplant Cyclophosphamide (PTCy) for prophylaxis against GVHD

5 days

In-patient treatment on days -2, -1, +1, +3, and +4

Follow-up

Participants are monitored for safety and effectiveness after treatment

27 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-Thymocyte globulin (rabbit)
• Cyclophosphamide

Trial Overview The study aims to compare the effectiveness of anti-thymocyte globulin (ATG) combined with cyclophosphamide versus ATG alone in preventing chronic graft-versus-host disease after stem cell transplantation in patients with specific blood disorders.

How Is the Trial Designed?

Group I: ATG/PTCy Experimental Treatment 2 Interventions

Anti-Thymocyte Globulin (ATG, Thymoglobulin) 4.5 mg/kg IV (divided 0.5, 2.0, 2.0 mg/kg on days -2, -1 and +1); cyclophosphamide (Post Transplant Cyclophosphamide, PTCy) 50 mg/kg IV daily on days +3 and +4.

Group II: ATG Active Control 1 Intervention

Anti-Thymocyte Globulin (ATG, Thymoglobulin) 4.5 mg/kg IV (divided 0.5, 2.0, 2.0 mg/kg on days -2, -1 and +1).

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Cell Therapy Transplant Canada

Collaborator

Trials

1

Recruited

80+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5286948/

Post-transplant cyclophosphamide versus anti-thymocyte ... Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04–2.02); ...

2. astctjournal.org astctjournal.org/article/S2666-6367(25)01322-3/fulltext

Effect of Anti-Thymocyte Globulin and Post-Transplant ... The combination of low-dose ATG (2 mg/kg) and PTCy reduces the risk of acute and chronic GVHD in F→M recipients, without increasing relapse risk ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3519/529515/A-Randomized-Pilot-Trial-Comparing-Anti-Thymocyte

A Randomized Pilot Trial Comparing Anti-Thymocyte Globulin ... Conclusion: The addition of PTCy to ATG did not result in excessive adverse events in this pilot trial (to day 100), and long-term results ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724001726

Outcomes of Antithymocyte Globulin-Post-Transplantation ... One-year overall survival (OS), nonrelapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) were 69.8%, 25.3%, and 52.0%, respectively, for patients ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2503189

Graft-versus-Host Disease Prophylaxis with ... GVHD-free, relapse-free survival at 3 years was 49% (95% CI, 36 to 61) with experimental prophylaxis and 14% (95% CI, 6 to 25) with standard ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12138436/

Efficacy and Safety of Combining r‐ATG With PTCy for ... The use of r‐ATG for GvHD prophylaxis has been proven effective in reducing the rates of graft rejection and acute GvHD (aGvHD) and chronic GvHD ...

7. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35365

Posttransplant cyclophosphamide versus anti‐thymocyte ... Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p = .003), worse leukemia-free survival (HR, 1.4; p = .