Treg Cells + IL-2 for Graft-versus-Host Disease

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: Glucocorticoids

Must not be taking: Calcineurin-inhibitors, Sirolimus

Disqualifiers: Active infection, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you need to be on a stable dose of glucocorticoids for 4 weeks before joining. You also cannot add or remove other immunosuppressive medications during that time.

What data supports the effectiveness of the treatment Treg Cells + IL-2 for Graft-versus-Host Disease?

Research shows that low-dose interleukin-2 (IL-2) can help increase the number of regulatory T cells (Tregs), which are important for controlling immune responses, and improve symptoms in patients with chronic graft-versus-host disease (GVHD). Studies also indicate that combining IL-2 with Treg infusions can effectively expand Tregs and reduce GVHD symptoms without causing harmful effects. ^{1 2 3 4 5}

Is the combination of Treg cells and IL-2 safe for treating graft-versus-host disease?

Studies show that low-dose interleukin-2 (IL-2) combined with regulatory T cells (Tregs) is generally safe for treating chronic graft-versus-host disease (cGVHD) in both adults and children. In children, it was well tolerated with positive responses, while adults experienced some dose-related challenges. Additionally, ultra-low dose IL-2 was well tolerated in healthy volunteers, indicating its general safety. ^{2 6 7 8 9}

How does the treatment Treg Cells + IL-2 for Graft-versus-Host Disease differ from other treatments?

This treatment is unique because it combines low-dose interleukin-2 (IL-2) with Treg-enriched infusions to specifically expand regulatory T cells (Tregs) in the body, which helps control graft-versus-host disease (GVHD) by enhancing the body's natural immune regulation without causing significant side effects. Unlike other treatments, this approach focuses on increasing the number and function of Tregs to suppress harmful immune responses while maintaining beneficial ones. ^{1 2 3 4 8}

What is the purpose of this trial?

This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. IL-2 is involved with cell signaling and regulation of white blood cells (WBCs). WBCs are part of the immune system. Treg cells are also part of the immune system; they are involved with anti-inflammatory responses. "Investigational" means that the combination of IL-2 and anti-inflammatory Treg cell infusion is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of IL-2 and anti-inflammatory Treg cell infusion for use in people with cGVHD. Chronic GVHD is a medical condition that may occur after you have received your bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease. Traditional standard therapy to treat cGVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigators are looking to assess the safety and optimal dose for the combination of IL-2 plus donor anti-inflammatory Treg cells, that may help control cGVHD by stopping the donor's immune system from 'rejecting' your body.

Research Team

John Koreth, MBBS, DPhil

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with chronic GVHD that hasn't improved with steroids. They must have had a stem cell transplant, be in fair health (ECOG 0-2), and not have changed their immunosuppressive meds or received new GVHD therapies recently. Pregnant women, breastfeeding individuals, those on certain drugs, or with active infections or other serious health issues can't join.

Inclusion Criteria

I have been on a stable dose of steroids for at least 4 weeks.

Agreement to use adequate contraception for the duration of study participation

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

Exclusion Criteria

I have a history of blood clotting disorders.

Other investigational drugs within 4 weeks prior to enrollment

Pregnant women or breastfeeding individuals

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Donor Lymphocyte Collection and Processing

Donor lymphocytes are collected and processed to enrich Treg cells for infusion

1 week

1 visit (in-person)

Treatment

Participants receive Treg-enriched donor lymphocyte infusion and daily IL-2 injections for 8 weeks

8 weeks

Weekly visits (in-person) for monitoring

Hiatus

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

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Visits every 4 weeks (in-person)

Extended-duration IL-2 Therapy (optional)

Participants may continue IL-2 treatment with evaluations every 4 weeks

Long-term

Visits every 4 weeks (in-person)

Treatment Details

Interventions

• Interleukin-2
• Treg-enriched infusion

Trial Overview The study tests the safety and optimal dose of IL-2 plus donor Treg cells to treat cGVHD by calming the immune response after a stem cell transplant. It's an early-phase trial to see if this combination can prevent the body from being 'rejected' by the donor's immune system.

Participant Groups

Group I: Treg-enriched infusion plus 8-week low-dose Interleukin-2 Experimental Treatment 2 Interventions

Treg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema. Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification).

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+

Miltenyi Biomedicine GmbH

Industry Sponsor

Trials

38

Recruited

1,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Iovance Biotherapeutics, Inc.

Industry Sponsor

Trials

26

Recruited

1,800+

Prometheus Laboratories

Industry Sponsor

Trials

27

Recruited

4,800+

References

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

Combined CD4+ donor lymphocyte infusion and low-dose recombinant IL-2 expand FOXP3+ regulatory T cells following allogeneic hematopoietic stem cell transplantation. [2021]

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

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

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

Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner. [2022]

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

Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo. [2023]

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

Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. [2021]

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

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

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

Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers. [2021]

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

A phase 1 study of donor regulatory T-cell infusion plus low-dose interleukin-2 for steroid-refractory chronic graft-vs-host disease. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Study protocol: Phase I/II trial of induced HLA-G+ regulatory T cells in patients undergoing allogeneic hematopoietic cell transplantation from an HLA-matched sibling donor. [2023]