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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for chronic graft-versus-host disease (cGVHD), a condition that can occur after a bone marrow or stem cell transplant. The treatment uses IL-2 (Interleukin-2, a protein that regulates immune cells) along with Treg cells (a type of immune cell that reduces inflammation) to determine if it can safely and effectively manage cGVHD. Suitable candidates are individuals who have undergone a stem cell transplant, experience ongoing cGVHD symptoms, and have not improved with standard steroid treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using IL-2 with donor Treg cells is generally safe and well-tolerated. In one study, patients with chronic graft-versus-host disease (cGVHD) who did not respond to steroid treatment managed these therapies well. After 8 weeks of therapy, 20% of the patients showed some improvement. Another study confirmed that taking a low dose of IL-2 daily, along with Treg cells, is safe for people with cGVHD.

While some side effects may occur, participants in the studies have managed them well. These findings come from early research, focusing primarily on safety rather than efficacy. However, they offer some reassurance about the treatment's safety in humans so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for graft-versus-host disease, which often involves immunosuppressive drugs like steroids, the treatment being studied combines Treg-enriched cell infusions with Interleukin-2 (IL-2). This approach is unique because it enhances the body's own regulatory T cells (Tregs) to better control the immune response, potentially reducing the harmful effects of the disease. Researchers are excited about this combination because it specifically targets and boosts the immune system's regulatory pathways, offering a more precise and potentially less toxic treatment option. By utilizing low-dose IL-2 to support Treg activity, this treatment could improve patient outcomes while minimizing side effects associated with broad immunosuppression.

What evidence suggests that this treatment might be an effective treatment for cGVHD?

In this trial, participants will receive a combination of Interleukin-2 (IL-2) and Treg (regulatory) cells to manage chronic graft-versus-host disease (cGVHD). Previous studies have shown that low-dose IL-2 effectively treats cGVHD, particularly in patients unresponsive to steroids, with over 50% experiencing improvement. Treg cells, which control inflammation, have also reduced the severity of cGVHD. Together, these treatments aim to calm the immune response, potentially reducing the body's self-attack. Early findings are encouraging, but further research is needed to confirm these benefits. ^{6 7 8 9 10}

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 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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3989436/

Ultra Low-Dose IL-2 for GVHD prophylaxis after Allogeneic ... This was a Phase II study to evaluate safety and efficacy of low-dose IL-2 in the prevention of severe (grade III or IV) acute GVHD in alloSCT recipients. We ...

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 ... While our results reflect only single-center experience, LD IL-2 has consistently been shown as a safe and effective therapy with 105 adult and ...

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/PMC9647832/

A phase 1 study of donor regulatory T-cell infusion plus low ... Treg DLI plus LD IL-2 was well tolerated and led to partial responses (PR) in 5 of 25 patients (20%) after 8 weeks of therapy. Ten additional ...

7. ashpublications.org ashpublications.org/bloodadvances/article-abstract/6/21/5786/485073

A phase 1 study of donor regulatory T-cell infusion plus low ... Infusion of healthy donor Treg followed by daily LD IL-2 is safe and well tolerated in patients with refractory cGVHD. · Daily LD IL-2 plus Treg ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01937468

NCT01937468 | Trial of Regulatory T-cells Plus Low-Dose ... 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 ...

9. clinicaltrial.be clinicaltrial.be/en/details/12237?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 f... Primary outcomes 1. Adverse event profile and the maximum tolerate dose of Treg-enriched infusion plus 8-week low-dose IL-2. Adverse events ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa1108188

Interleukin-2 and Regulatory T Cells in Graft-versus-Host ... Daily low-dose interleukin-2 was safely administered in patients with active chronic GVHD that was refractory to glucocorticoid therapy.