IL-2 for Chronic Graft-versus-Host Disease

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

35 Participants Needed

Trial Summary

What is the purpose of this trial?

Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like calcineurin-inhibitors with sirolimus. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Interleukin-2 for treating chronic graft-versus-host disease?

Research shows that low-dose Interleukin-2 can increase regulatory T cells, which help control the immune response, and has been effective in reducing symptoms of chronic graft-versus-host disease in some patients. In one study, patients receiving low-dose Interleukin-2 had a lower incidence of moderate-to-severe chronic graft-versus-host disease compared to those who did not receive it. ^{1 2 3 4 5}

Is IL-2 generally safe for use in humans?

IL-2, also known as Interleukin-2 or Aldesleukin, has been used in cancer treatment and studied for other conditions, but it can cause side effects due to its impact on the immune system. Studies suggest that low-dose IL-2 is safe for children with chronic graft-versus-host disease, but adults may experience more side effects at higher doses. ^{4 6 7 8 9}

How does the drug IL-2 differ from other treatments for chronic graft-versus-host disease?

IL-2 is unique because it helps increase the number of regulatory T cells (Tregs), which are important for controlling the immune response and reducing chronic graft-versus-host disease. This approach is different from other treatments that may not specifically target Tregs. ^{1 2 10 11 12}

Research Team

John Koreth, MBBS, DPhil

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for people who have chronic graft-versus-host disease (cGVHD) after a stem cell transplant and haven't responded to steroids. They should have started systemic therapy within the last 6 months, had no more than two prior cGVHD treatments, and must have good organ function. It's not for those with HIV on antiretrovirals, active hepatitis B or C, certain drug combinations, cancer relapse, uncontrolled infections or heart issues.

Inclusion Criteria

I have received a stem cell transplant from a donor.

I have had 2 or fewer treatments for chronic GVHD.

My chronic GVHD hasn't improved with steroids, started treatment within the last 6 months.

Exclusion Criteria

I take more than 1 mg/kg/day of prednisone or its equivalent.

I am currently taking calcineurin inhibitors and sirolimus.

I do not have uncontrolled heart pain or symptoms of heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous IL-2 for 12 weeks, with concurrent steroid treatment for the first 6 weeks

12 weeks

Clinic visits every 4 weeks, immunologic assays every 8 weeks

Hiatus

Participants have a 4-week break from IL-2 treatment

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Open-label extension (optional)

Participants may continue extended-duration IL-2 treatment if they experience clinical benefit

Indefinite

Treatment Details

Interventions

• Interleukin-2

Trial Overview The study tests Interleukin-2 (IL-2) combined with steroids in treating cGVHD. Researchers want to see if IL-2 can prevent the donor's immune system from attacking the recipient's body by controlling this rejection process known as cGVHD.

Participant Groups

Group I: Interleukin-2 Experimental Treatment 1 Intervention

Each study participant will receive daily subcutaneous IL-2 (1 x 106 IU/m2/day) for self-administration for 12 weeks, followed by a 4-week hiatus. IL-2 will be typically administered on an outpatient basis. After completing the 16 week study (12 weeks of IL-2 study treatment and a mandatory 4 weeks off-IL-2), patients experiencing clinical benefit (complete or partial response; as well as minor response not meeting NIH criteria for partial response) with an acceptable toxicity profile will be permitted to continue extended-duration treatment indefinitely at the discretion of the treating physician.

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Prometheus Laboratories

Industry Sponsor

Trials

27

Recruited

4,800+

Findings from Research

In a study of 90 allogeneic hematopoietic stem cell transplant recipients, low-dose interleukin-2 (IL-2) administration did not significantly reduce leukemia relapse rates but was associated with a higher rate of GVHD-free survival (47% vs. 31% in the control group).

Patients receiving IL-2 showed a lower incidence of moderate-to-severe chronic graft-versus-host disease (cGVHD) compared to the control group (33% vs. 57%), indicating that IL-2 may help mitigate this common post-transplant complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study. Zhao, XY., Zhao, XS., Wang, YT., et al.[2021]

BAY 50-4798, a novel IL-2 analog, shows similar potency to aldesleukin in stimulating T cell proliferation but with significantly reduced inflammatory responses, indicating a potentially safer profile for patients.

In studies comparing cytokine responses, BAY 50-4798 induced about 5-fold lower levels of endogenous IL-2 and at least 50% lower levels of proinflammatory cytokines compared to aldesleukin, suggesting it may have fewer side effects in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. Steppan, S., Eckart, MR., Bajsarowicz, K., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

A review of low dose interleukin-2 therapy in management of chronic graft-versus-host-disease. [2023]

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

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study. [2021]

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

Organ-specific response after low-dose interleukin-2 therapy for steroid-refractory chronic graft-versus-host disease. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin 2. [2019]

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

Interleukin-2 and regulatory T cells in graft-versus-host disease. [2022]

6. England pubmed.ncbi.nlm.nih.gov

IL-2-induced GVHD protection is not inhibited by cyclosporine and is maximal when IL-2 is given over a 25 h period beginning on the day following bone marrow transplantation. [2013]

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

Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. [2013]

8. Israel pubmed.ncbi.nlm.nih.gov

Radiosensitivity and responsiveness to recombinant interleukin-2 of effector cells of graft vs. host disease and mixed lymphocyte reaction in mice. [2006]

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

Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children. [2021]

10. Turkey pubmed.ncbi.nlm.nih.gov

T-helper-1 (Th1) and Th2 cytokines after allogeneic hematopoietic stem cell transplantation (allo-HSCT). [2016]

11. China pubmed.ncbi.nlm.nih.gov

Roles of interleukin-10 in acute graft-versus-host disease and graft rejection. [2006]

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

Interleukin-10 modulation of alloreactivity and graft-versus-host reactions. [2019]