ATG Combination Therapy for Acute GVHD

Overseen By Margaret A Thomas, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Investigational drugs

Disqualifiers: HIV, Non-hematologic malignancy, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment mix to prevent or lessen the severity of graft-versus-host disease (GVHD), which can occur after a stem cell transplant. The treatment combines the drugs tacrolimus and methotrexate with a new dosing strategy for rabbit Anti-thymocyte Globulin (ATG, also known as Thymoglobulin). This trial targets individuals with acute myeloid leukemia or other specific blood disorders who have a matched donor for a stem cell transplant. Ideal participants are those in complete remission but at high risk of relapse. The goal is to determine if this combination can improve outcomes one year after a transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 has shown that Anti-thymocyte Globulin (ATG) is generally safe for patients. Studies have found that ATG reduces the risk of both short-term and long-term GVHD, a type of transplant rejection, without increasing the chance of disease recurrence. As a result, patients taking ATG often experience fewer GVHD-related issues compared to those who do not.

In various studies, patients tolerated ATG well at low to medium doses, experiencing fewer serious side effects. Although some patients may still encounter side effects, ATG is considered safe for preventing GVHD. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for GVHD?

Unlike the standard of care for acute graft-versus-host disease (GVHD), which typically includes Tacrolimus and Methotrexate, this investigational treatment introduces a two-step dosing of Anti-Thymocyte Globulin (ATG). Researchers are excited about this approach because it has the potential to significantly improve the one-year GVHD-free survival rate from 35% to 60%. This combination therapy aims to better prevent GVHD by targeting T-cells more effectively, reducing the risk of severe complications post-transplant.

What evidence suggests that this combination therapy could be effective for acute GVHD?

Research has shown that Anti-thymocyte Globulin (ATG), administered to participants in this trial, reduces the chances of both short-term and long-term graft-versus-host disease (GVHD). Studies have found that ATG significantly lowers the risk of severe GVHD and improves overall survival rates in patients. Specifically, one study discovered that patients treated with ATG had a higher chance of surviving without severe GVHD or relapse compared to those who did not receive ATG. These findings suggest that ATG plays a crucial role in preventing and managing GVHD. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with conditions like Myelodysplastic Syndrome, Preleukemia, or Acute Leukemia who are undergoing a myeloablative allogeneic stem cell transplant. The goal is to prevent acute Graft-versus-Host Disease (GVHD). Specific eligibility criteria details were not provided.

Inclusion Criteria

Calculated creatinine clearance greater than 50 mL/minute

I can carry out normal activities with minimal symptoms.

My liver tests are within the required range.

Exclusion Criteria

Pregnant and/or breastfeeding

Participation in another clinical study with an investigational product during the last 28 days

Known hypersensitivity to the study agent (ATG)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 2-step ATG dosing regimen combined with tacrolimus and mini methotrexate to prevent acute GVHD post myeloablative allogeneic stem cell transplant

1 week

Multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immune cell recovery and GVHD prevention

1 year

Regular visits for immune monitoring

What Are the Treatments Tested in This Trial?

Interventions

• ATG

Trial Overview The study tests if using Anti-thymocyte Globulin (ATG) in a new dosing strategy along with Tacrolimus and Mini Methotrexate can prevent or lessen the severity of acute and/or chronic GVHD after stem cell transplant.

How Is the Trial Designed?

Group I: phase II single arm study of 2 step ATG dosing in prevention of aGVHD. Experimental Treatment 1 Intervention

The primary outcome for the study is rate of GRFS at one-year post transplant. When accounting for competing risks, any death, relapse, Grade III-IV acute GVHD and cGVHD requiring systemic therapy are competing risks. The reported one year GRFS with the use of standard of care GVHD prevention regimen in MA HSCT (Tac/MTX) was 35%. (El-Jurdi 2023) We hypothesize that with 2 step ATG/Tac/Mini MTX regimen, we can achieve a one year GRFS of 60%.

ATG is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Approved in European Union as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Approved in Canada as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Thymoglobulin is a safe and effective treatment for preventing acute rejection in organ transplantation, with common side effects including cytokine release syndrome and thrombocytopenia, but recent studies suggest that antiviral prophylaxis can mitigate the risk of cytomegalovirus disease associated with its use.

Thymoglobulin may offer advantages over horse ATG in treating aplastic anemia and can reduce the incidence of acute and chronic graft-versus-host disease (GvHD) in patients receiving stem cell transplants, indicating its potential as a versatile immunosuppressant in various therapeutic contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymoglobulin--new approaches to optimal outcomes. Moicean, AD., Popp, AM., Sinescu, I.[2021]

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 209 patients undergoing allogenic hematopoietic cell transplantation, a single low dose of anti-thymocyte globulin (ATG) significantly reduced the incidence of chronic graft versus host disease (cGVHD) compared to those who did not receive ATG, with rates of 10.1% versus 25%.

Despite the reduction in cGVHD, the use of low dose ATG did not affect overall survival or relapse-free survival rates, indicating that it may be a safe option to minimize cGVHD without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes with low dose anti-thymocyte globulin in patients undergoing matched unrelated donor allogeneic hematopoietic cell transplantation. Mountjoy, L., Jain, T., Kunze, KL., et al.[2021]

In a multicenter phase II study involving 77 patients undergoing HLA-matched peripheral blood stem cell transplantation (PBSCT), low-dose anti-thymocyte globulin (ATG) significantly reduced the incidence of severe acute graft-versus-host disease (GVHD) to just 1.4% at 100 days, well below the predefined threshold of 18%.

The study also reported a low incidence of chronic GVHD at one year, with only 15.3% of patients experiencing all-grade chronic GVHD and 5.6% experiencing moderate to severe cases, indicating that low-dose ATG is effective in minimizing both acute and chronic GVHD risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose anti-thymocyte globulin for GVHD prophylaxis in HLA-matched allogeneic peripheral blood stem cell transplantation. Shiratori, S., Sugita, J., Ota, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5286931/

Anti-thymocyte globulin as graft-versus-host disease ... This article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells.

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

Effect of Anti-Thymocyte Globulin and Post-Transplant ... In conclusion, the combination of ATG and PTCy appears to significantly reduce the incidence of chronic GVHD without increasing relapse risk in ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712311593X

Effectiveness and Safety of Rabbit Anti-Thymocyte Globulin ... rATG demonstrated significant reductions in the incidence of both aGVHD and cGVHD and increased the overall survival across donor types and stem cell sources.

4. karger.com karger.com/aha/article/doi/10.1159/000541071/912502/Real-world-impact-of-routine-addition-of-anti

Real-World Impact of Routine Addition of Antithymocyte ... The severe GVHD-relapse-free survival was higher in the ATG group (36.4%) than the control (12.9%; p < 0.001). Nevertheless, the 2-year overall ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5735843/

ATG Prevents Severe Acute Graft-versus-Host Disease in ... The efficacy of anti-thymocyte globulin (ATG) in the prevention of both aGVHD and cGVHD is supported by evidence including retrospective comparative data ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4992/500995/Effectiveness-and-Safety-of-Rabbit-Anti-Thymocyte

Effectiveness and Safety of Rabbit Anti-Thymocyte Globulin ... This study assessed the effectiveness and safety of rATG relative to non-ATG prophylaxis regimens for acute GVHD (aGVHD) or chronic GVHD (cGVHD) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7061010/

Clinical impact of anti-thymocyte globulin on survival and ... The results of this study suggested that low to medium dose of ATG (2.5 to 7.5 mg/kg) would be adequate for better GVHD prophylaxis and better survival outcomes ...