ATG Dosing for Blood Cancer

Overseen By Zaid Al Kadhimi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must be taking: Tacrolimus, Methotrexate

Must not be taking: Investigational drugs

Disqualifiers: HIV, Cirrhosis, 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: 6

Duration: 1 week

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering ATG (Anti-Thymocyte Globulin) to assist individuals with certain blood cancers undergoing a stem cell transplant. The goal is to prevent graft versus host disease (GVHD) and improve survival without cancer recurrence. The trial employs a two-step dosing schedule for ATG, alongside other standard medications, to determine if it offers better protection against severe GVHD. Suitable candidates for this trial include those with blood cancers, such as specific types of leukemia or myelodysplastic syndromes, who are receiving a stem cell transplant from a matched donor. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received any investigational drugs within 14 days prior to the first day of transplant conditioning.

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 and well-tolerated. Studies have found that ATG effectively reduces both short-term and long-term graft-versus-host disease (GVHD) without increasing the risk of cancer recurrence. This finding is significant because ATG can protect the body after a stem cell transplant without causing additional harm.

ATG has been linked to better survival rates and a lower chance of GVHD, which can be serious after transplants. It has been tested in various doses, and even small amounts have effectively reduced these risks. Overall, these studies suggest that ATG is safe for patients undergoing treatments like transplants, aiming to improve outcomes while minimizing harmful effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the ATG treatment for blood cancer because it offers a new approach to preventing acute graft-versus-host disease (aGVHD) post-transplant. Unlike the current standard treatments, which often include drugs like PTCY, tacrolimus, and MMF, this treatment uses a 2-step ATG dosing regimen combined with tacrolimus and mini methotrexate. This innovative method aims to improve the one-year graft-versus-host disease-free survival (GRFS) rate significantly, potentially increasing it from 52% to 69%. The unique dosing strategy of ATG is what sets it apart, offering hope for better outcomes for patients undergoing transplants.

What evidence suggests that this ATG dosing is effective for preventing GVHD?

Research has shown that anti-thymocyte globulin (ATG) can lower the risk of graft versus host disease (GVHD) after stem cell transplants. One study found that ATG significantly reduced both short-term and long-term GVHD while increasing survival chances. Another study discovered that using ATG with other treatments decreased long-term GVHD without raising the risk of cancer returning. Early results from a specific ATG dosing plan, currently tested in this trial, showed promise in preventing severe GVHD and aiding immune system recovery. The evidence suggests that ATG plays a crucial role in making stem cell transplants safer and more effective for blood cancer patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Zaid Al Kadhimi, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for individuals with acute leukemia, myeloproliferative disorders, preleukemia, or myelodysplastic syndromes who are undergoing allogeneic stem cell transplant. The study aims to prevent severe graft versus host disease (GVHD). Specific eligibility criteria details were not provided.

Inclusion Criteria

Willingness to sign informed consent and abide by protocol requirements

My lung function tests show at least half the normal capacity.

My liver tests are within the required range.

Exclusion Criteria

I had a stem cell transplant using my own cells less than 3 months ago.

I have had a stem cell transplant from a donor.

Known hypersensitivity to study agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 step ATG dosing combined with tacrolimus and mini methotrexate for prevention of acute GVHD

1 week

Multiple visits for ATG administration on days -6, -5, -4, and -1

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on GVHD/relapse free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• ATG

Trial Overview The trial tests a new way of giving anti-thymocyte globulin (ATG) in two steps before the transplant to reduce GVHD while improving immune response and survival without relapse or GVHD at one year post-transplant. It's combined with standard tacrolimus and mini methotrexate.

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 GRFS rate at one-year post transplant. GRFS will be estimated using Kaplan Meier method The reported GRFS with recent phase III trial of PTCY/tac/MMF in transplant from matched related and unrelated donors at 1 year follow up was 52%. We hypothesize that with 2 step ATG/Tac/Mini MTX regimen, we can achieve a one year GRFS of 69%.

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

In a study of 29 patients receiving anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) for aplastic anemia, 62.1% experienced adverse effects, with fever being the most common.

ATG, which is rabbit-derived, was associated with more frequent adverse effects compared to ALG, and shorter intervals between treatment cycles increased the risk of these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adverse effects of anti-thymocyte globulin/anti-lymphocyte globulin therapy]. Kobayashi, R., Kaneda, M., Watanabe, N., et al.[2006]

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 of 24 patients with aplastic anemia, the survival rates at 6 months varied among different anti-thymocyte globulin (ATG) preparations, with Lymphoglobulin showing the highest survival rate at 77.8%.

None of the patients treated with ATG-Fresenius (ATG-F) responded to the treatment, indicating it is significantly less effective and should not be used for severe aplastic anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of Jurkat cell-reactive anti-T lymphocyte globulin and fetal anti-thymocyte globulin preparations in the treatment of aplastic anemia. Serefhanoglu, S., Buyukasik, Y., Purnak, T., et al.[2011]

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. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/bjh.70124

A decade of experience using ATG and PTCy for graft‐ ... Graft-versus-host disease-free, relapse-free survival (GRFS) at 24 months was 49% (95% CI: 44–53), and overall survival (OS) was 68.3% (95% CI: ...

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 ...