ECP + Low-Dose IL-2 for Graft-versus-Host Disease

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Corticosteroids

Must not be taking: Antiretrovirals, Calcineurin-inhibitors, Sirolimus, others

Disqualifiers: Active infection, Malignant relapse, Organ transplant, 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: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with chronic graft-versus-host disease (GVHD), a condition that can occur after a stem cell transplant when donated cells attack the recipient's body. The trial combines Extracorporeal Photopheresis (ECP) with Interleukin-2 (IL-2) to determine if it can better manage symptoms for those unresponsive to steroids. Individuals who have undergone a stem cell transplant and continue to experience GVHD symptoms despite steroid treatment might be suitable for this study. As a Phase 2 trial, the 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 requires that you have a stable dose of corticosteroids and no changes to other immunosuppressive medications for 4 weeks before joining. You cannot use certain combinations of medications, like calcineurin-inhibitors with sirolimus, and must avoid new immunosuppressive drugs before starting the trial.

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

Research shows that extracorporeal photopheresis (ECP) is generally safe for patients with graft-versus-host disease (GVHD). ECP processes blood outside the body to help manage the disease. Studies indicate that it is well-tolerated and effective for both acute and chronic GVHD.

Combining ECP with a low dose of interleukin-2 (IL-2) maintains a positive safety profile. IL-2 strengthens the immune system. Research shows that this combination has been safe for more than 60% of patients with chronic GVHD unresponsive to steroids. This suggests the treatment is both helpful and safe for many individuals. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for GVHD?

Researchers are excited about the combination of Extracorporeal Photopheresis (ECP) and low-dose Interleukin-2 (IL-2) for treating Graft-versus-Host Disease because it offers a unique approach to modulating the immune system. Unlike standard treatments that primarily suppress immune activity, this combination therapy aims to enhance regulatory T cells, potentially leading to a more balanced immune response. ECP is already a standard-of-care procedure that safely alters immune cells outside the body, and adding low-dose IL-2 could selectively boost beneficial immune cells without the intensity of traditional immune suppression. This dual approach may offer a more targeted and potentially less toxic alternative to existing therapies.

What evidence suggests that ECP plus IL-2 could be an effective treatment for chronic GVHD?

Studies have shown that using extracorporeal photopheresis (ECP) with low-dose interleukin-2 (IL-2) can improve chronic graft-versus-host disease (GVHD). This trial will evaluate the combination of ECP and IL-2, which boosts certain immune cells, called Treg and NK cells, that help control inflammation. Research indicates that patients with chronic GVHD have experienced improvement when treated with low-dose IL-2. ECP is already known to be safe and effective for treating GVHD. Together, ECP and IL-2 show promising results for managing this condition. ^{4 5 6 7 8}

Who Is on the Research Team?

John Koreth, MBBS,D.Phil

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic graft-versus-host-disease (cGVHD) after a stem cell transplant from a closely matched donor. They must have cGVHD that hasn't improved with steroids, stable medication use for the past month, and good organ function. Pregnant women, those with certain blood disorders or infections, recent ECP therapy or exposure to new immunosuppressants can't participate.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

You are expected to live for more than 3 months.

My corticosteroid dose has been the same for the last 4 weeks.

Exclusion Criteria

I am currently taking calcineurin inhibitors and sirolimus.

I need more than 1 mg/kg/day of prednisone.

I have a history of blood clotting disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care ECP treatment two times a week for 16 weeks. Starting after Week 8, IL-2 is administered daily for 8 weeks.

16 weeks

2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extension

Participants may continue ECP and IL-2 therapy if chronic GVHD improves at the end of the 16-week study duration.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Extracorporeal Photopheresis (ECP)
• Interleukin-2

Trial Overview The study is testing if adding low-dose Interleukin-2 (IL-2) to Extra-corporeal Photopheresis (ECP), a light-based treatment, can help treat cGVHD better than ECP alone. Participants will receive both treatments and be monitored to see how well they respond compared to their condition before starting the trial.

How Is the Trial Designed?

Group I: ECP plus IL-2 Experimental Treatment 2 Interventions

* Extracorporeal Photopheresis (ECP) standard-of-care * Daily subcutaneous (SC) interleukin-2 (IL-2) (Proleukin®) during predetermined weeks of treatment cycle

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Prometheus Laboratories

Industry Sponsor

Trials

27

Recruited

4,800+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30936057/

Efficacy and immunologic effects of extracorporeal ... - PubMed We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential Treg and NK-cell expansion ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03007238

Extracorporeal Photopheresis and Low Dose Aldesleukin ... This phase II trial studies efficacy of extracorporeal photopheresis and low dose aldesleukin (interleukin-2) in treating patients with chronic ...

3. ashpublications.org ashpublications.org/bloodadvances/article/3/7/969/247277/Efficacy-and-immunologic-effects-of-extracorporeal

Efficacy and immunologic effects of extracorporeal ... We demonstrated that low-dose interleukin-2 (IL2) led to clinical improvement in SR-cGVHD and stimulated preferential Treg and NK-cell expansion ...

4. nature.com nature.com/articles/s41375-022-01701-2

Extracorporeal photopheresis in acute and chronic steroid‑ ... Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019;3 ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/1744666X.2023.2295405

Recent insights into extracorporeal photopheresis for graft- ... Considering the high safety profile and proven efficacy reported in studies to date, ECP has been used in an attempt to prevent acute and chronic GvHD.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03007238?term=AREA%5BConditionSearch%5D(%22Bronchiolitis%20Obliterans%22)%20AND%20AREA%5BInterventionSearch%5D(%22Analgesics%22)&rank=7

Extracorporeal Photopheresis and Low Dose Aldesleukin ... This phase II trial studies efficacy of extracorporeal photopheresis and low dose aldesleukin (interleukin-2) in treating patients with chronic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11510389/

Safety and Efficacy of Extracorporeal Photopheresis for ... Our data confirm that ECP is a safe and effective treatment option for patients with acute and chronic GVHD and it is associated with an ...

8. astctjournal.org astctjournal.org/article/S2666-6367(23)01385-4/fulltext

Extracorporeal Photopheresis in Graft-versus-Host Disease Extracorporeal photopheresis has shown efficacy in graft-versus-host disease. Recent observations are offering newer insights into its mechanism of action.