Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease

Chronic Graft-versus-host Disease Clinical Trial

Official title:

A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01366092
• Other study ID #: 11-149
• Secondary ID: P01CA142106
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 2011
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD.

Description:

You will give yourself or be given IL-2 daily through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 12 weeks. You will then have 4 weeks off of IL-2. During the first 6 weeks of IL-2, you will continue to take steroids without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.

While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system.

You will have clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks. You will also have immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.

You will be on the study for about 16 weeks. You may continue on study treatment for longer if you experience a clinical benefit.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: December 2024
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recipient of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens

• Steroid refractory cGVHD with systemic therapy onset within the prior 6 months

• No more than 2 prior lines of cGVHD therapy

• Estimated life expectancy > 3 months

• Adequate organ function

Exclusion Criteria:

• Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)

• Concurrent use of calcineurin-inhibitors plus sirolimus

• History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura

• Active malignant relapse

• Active uncontrolled infection

• Uncontrolled cardiac angina or symptomatic congestive heart failure

• Organ transplant (allograft) recipient

• HIV-positive on combination antiretroviral therapy

• Active hepatitis B or C

• Pregnant or breast-feeding

Related Conditions & MeSH terms

• Bronchiolitis Obliterans Syndrome
• Chronic Graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• Interleukin-2
Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	National Cancer Institute (NCI), Prometheus Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD	Participants were evaluated according to the cGVHD NIH Consensus criteria at baseline, 6 weeks, and 12 weeks on study. Per cGVHD NIH Consensus criteria, cGVHD involved organ systems are given a grade 0-3 and an overall cGVHD score, from 0-10, is given. Complete Response is defined as resolution of all reversible manifestations in each organ or site of cGVHD. A partial response is defined as an improvement in measure at least one organ or site, or decrease in global ratings by at least a 2-point change on the 10-point scale, without progression measured at any other organ or site. Non-responders have no change in cGVHD meeting criteria for either partial response or disease progression. Progressive disease is defined as an increase in organ or site scales (1-point change on a 3-point scale) or 2- to 3-point increase on the global cGVHD ratings. Clinical worsening of cGVHD is not synonymous with progressive cGVHD per NIH criteria.	Baseline, 6 weeks, and 12 weeks
Secondary	Toxicity of 12-week Course of Low-dose SC IL-2 Therapy	Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course	12 weeks
Secondary	Prednisone Taper With IL-2 Therapy	Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.	End of treatment after 16 weeks or most recent follow-up date for patients on extended
Secondary	Overall Survival and Progression-free Survival	Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. OS was defined as from the study entry to death from any cause. Patients who were alive or lost to follow-up were censored at the time last seen alive. PFS was defined from the study entry to disease relapse or progression or death from any cause, whichever occurred first.	2 years from start of IL-2
Secondary	Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts	Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The CD4+CD25+FOXP3+ regulatory T cells (Treg) counts were measured.	16 weeks of study follow-up
Secondary	Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio	Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The ratio between CD4+CD25+FOXP3+ regulatory T cells (Treg) and CD4 conventional T cell (Tcon) counts were measured.	16 weeks of study follow-up