Clinical trial NCT01366092: Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
Official title: A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Graft-versus-host Disease
Keywords: stem cell transplant
GVHD
bone marrow transplant
cord blood transplant
regulatory T cell
interleukin
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Prometheus Laboratories
First posted: 2011-06-03
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD
timeFrame: Baseline, 6 weeks, and 12 weeks
Secondary outcomes:
measure: Toxicity of 12-week Course of Low-dose SC IL-2 Therapy
timeFrame: 12 weeks
measure: Prednisone Taper With IL-2 Therapy
timeFrame: End of treatment after 16 weeks or most recent follow-up date for patients on extended
measure: Overall Survival and Progression-free Survival
timeFrame: 2 years from start of IL-2
measure: Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts
timeFrame: 16 weeks of study follow-up
measure: Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio
timeFrame: 16 weeks of study follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: John Koreth, MBBS, DPhil
role: PRINCIPAL_INVESTIGATOR
References: