IL-2 for Chronic Graft-versus-Host Disease

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Steroids

Must not be taking: Calcineurin-inhibitors, Sirolimus

Disqualifiers: Active infection, Cardiac issues, HIV, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether IL-2 (Interleukin-2), a type of medication, can help manage chronic graft-versus-host disease (GVHD). This condition occurs after a bone marrow or stem cell transplant when the donor's immune system attacks the recipient's body. The study combines IL-2 with steroids to determine if it can better control this immune response. Individuals who have undergone a stem cell transplant and are experiencing chronic GVHD that hasn't improved with other treatments might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that IL-2 is likely to be safe for humans?

Research has shown that low-dose Interleukin-2 (IL-2) is generally safe and well-tolerated in people with chronic graft-versus-host disease (GVHD). Studies indicate that many patients respond positively to this treatment. For instance, one study found that after 8 to 12 weeks of treatment, about 49% to 53% of patients improved. Importantly, low-dose IL-2 has been safely used in both adults and children with advanced cases of the disease, suggesting that the treatment is manageable for many, with few serious side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic graft-versus-host disease, which often involve steroids and immunosuppressants, Interleukin-2 (IL-2) offers a novel approach by enhancing the body's regulatory T-cells. This unique mechanism helps balance the immune response, potentially reducing harmful inflammation without broadly suppressing immunity. Researchers are excited about IL-2 because it targets the root of the problem, offering the possibility of long-term relief with fewer side effects than current options. Plus, its self-administration method makes it convenient for patients, allowing them to maintain their normal routines.

What evidence suggests that IL-2 might be an effective treatment for chronic GVHD?

Research has shown that low-dose Interleukin-2 (IL-2), which participants in this trial will receive, can help treat chronic graft-versus-host disease (cGVHD), especially when steroids alone aren't effective. Studies have found that more than half of the patients who received low-dose IL-2 experienced improvements, with long-lasting control of the disease. This treatment is generally well-tolerated, with most patients not experiencing severe side effects. In children and young patients, IL-2 has successfully reduced some symptoms of cGVHD. Overall, evidence suggests that IL-2 could be a promising option for managing this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

John Koreth, MBBS, DPhil

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 am HIV-positive and on combination antiretroviral therapy.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10448399/

More evidence for low-dose IL-2 for chronic GVHD in children Wobma et al report that subcutaneous low-dose interleukin-2 (LD IL-2) reversed chronic graft-versus-host disease (cGVHD) manifestations in children and young ...

2. ashpublications.org ashpublications.org/blood/article/128/1/130/35356/Efficacy-durability-and-response-predictors-of-low

Efficacy, durability, and response predictors of low-dose ... Low-dose IL-2 is efficacious in steroid-refractory cGVHD, with objective responses in >50% of patients, and durable disease control. IL-2 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952923002781

Real-world experience with low-dose IL-2 for children and ... Low-dose IL-2 is safe and well tolerated at variable dosing regimens in pediatric patients with steroid-refractory chronic GVHD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00529035

Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft ... The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic ...

5. gvhdhub.com gvhdhub.com/medical-information/the-safety-and-efficacy-of-low-dose-interleukin-2-for-the-treatment-of-sr-cgvhd

The safety and efficacy of low-dose interleukin-2 for ... Overall response rate was evaluated after either 8 or 12 weeks of LD IL-2 therapy and was found to be 48.6% and 53.3%, respectively. Fewer prior ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10448423/

Real-world experience with low-dose IL-2 for children and ... Low-dose IL-2 is safe and well tolerated at variable dosing regimens in pediatric patients with steroid-refractory chronic GVHD. Low-dose IL-2 is effective ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00529035

Study Details | NCT00529035 | Ultra-Low Dose Interleukin- ... The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic ...

8. ashpublications.org ashpublications.org/bloodadvances/article/3/17/2550/261399/Dose-escalated-interleukin-2-therapy-for

Dose-escalated interleukin-2 therapy for refractory chronic ... We show for the first time that low-dose IL-2 is safe in children with advanced SR cGVHD and can lead to clinically meaningful responses while ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6737411/

Dose-escalated interleukin-2 therapy for refractory chronic ... We show for the first time that low-dose IL-2 is safe in children with advanced SR cGVHD and can lead to clinically meaningful responses while ...