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

25 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment ECP + Low-Dose IL-2 for Graft-versus-Host Disease?

Research shows that the combination of ECP (a treatment that modifies blood cells outside the body) and low-dose IL-2 (a protein that helps regulate the immune system) is effective in treating chronic graft-versus-host disease. In a study, 62% of patients showed improvement after receiving both treatments, compared to 29% with ECP alone, indicating that adding IL-2 enhances the treatment's effectiveness. ^{1 2 3 4 5}

Is ECP + Low-Dose IL-2 safe for humans?

Extracorporeal photopheresis (ECP) has been used safely in treating graft-versus-host disease and other T-cell mediated conditions, with few and not serious side effects. While specific safety data for the combination with low-dose IL-2 is not detailed, ECP alone is generally considered safe. ^{1 2 4 6 7}

How is the ECP + Low-Dose IL-2 treatment for graft-versus-host disease different from other treatments?

The ECP + Low-Dose IL-2 treatment is unique because it combines extracorporeal photopheresis (a procedure that treats blood outside the body) with low-dose interleukin-2, which helps increase regulatory T-cells that can reduce inflammation and immune response. This combination aims to manage graft-versus-host disease by enhancing immune regulation without the high toxicity associated with other treatments. ^{8 9 10 11 12}

What is the purpose of this trial?

This research study is evaluating a combination of a therapy called Extra-corporeal Photopheresis (ECP) with a drug called Interleukin-2 (IL-2) as a possible treatment for chronic graft-versus-host-disease (GVHD) following allogeneic stem cell transplant.

Research Team

John Koreth, MBBS,D.Phil

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Lymphocytes treated by extracorporeal photopheresis can down-regulate cytokine production in untreated monocytes. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Extracorporeal photopheresis in the management of graft-versus-host disease. [2021]

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

Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. [2020]

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

Extracorporeal photopheresis attenuates murine graft-versus-host disease via bone marrow-derived interleukin-10 and preserves responses to dendritic cell vaccination. [2021]

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

Extracorporeal photopheresis reduces the number of mononuclear cells that produce pro-inflammatory cytokines, when tested ex-vivo. [2018]

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

In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis. [2021]

7. Denmark pubmed.ncbi.nlm.nih.gov

[Documented effect of extra corporeal photopheresis on T-cell mediated diseases]. [2013]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Interleukin-2 in bone marrow transplantation: preclinical studies. [2007]

10. China pubmed.ncbi.nlm.nih.gov

[TNF-alpha production and antitumor effect of rhIL-2-activated bone marrow cells]. [2006]

11. Germany pubmed.ncbi.nlm.nih.gov

Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. [2015]

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

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