Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease|
- Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD [ Time Frame: Baseline, 6 weeks, and 12 weeks ] [ Designated as safety issue: No ]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.
- Toxicity of 12-week Course of Low-dose SC IL-2 Therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course
- Prednisone Taper With IL-2 Therapy [ Time Frame: End of treatment after 16 weeks or most recent follow-up date for patients on extended ] [ Designated as safety issue: No ]Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.
- Overall Survival and Progression-free Survival [ Time Frame: 2 years from start of IL-2 ] [ Designated as safety issue: No ]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.
- Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts [ Time Frame: 16 weeks of study follow-up ] [ Designated as safety issue: No ]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.
- Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio [ Time Frame: 16 weeks of study follow-up ] [ Designated as safety issue: No ]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.
|Study Start Date:||July 2011|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Other Name: IL-2
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01366092
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02214|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02214|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||John Koreth, MBBS, DPhil||Dana-Farber Cancer Institute|