Clinical trial NCT00529035: Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft Versus Host Disease
Official title: A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft Versus Host Disease
Keywords: Chronic GVHD
Steroid refractory GVHD
allogeneic stem cell transplantation
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Novartis
First posted: 2007-09-14
Enrollment: 29
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: 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 graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.

Detailed description: * IL-2 will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels.
* Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.

Eligibility criteria: Inclusion Criteria:

* Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
* Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
* Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months without complete resolution of signs and symptoms.
* Stable dose of corticosteroids for 4 weeks prior to enrollment
* No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment.
* Adequate bone marrow, renal and hepatic function as outlined in the protocol
* 18 years of age or older
* ECOG Performance Status of 0-2

Exclusion Criteria:

* Ongoing prednisone requirement \> 1mg/kg/day (or equivalent)
* Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
* Concurrent ECP therapy within 4 weeks prior to enrollment
* Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
* Donor lymphocyte infusion within 100 days prior to IL-2 therapy
* Active malignant disease relapse
* Active, uncontrolled infection
* Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
* HIV seropositivity
* Life expectancy \< 3 months
* Pregnancy or lactation
* Inability to comply with IL-2 treatment regimen
* Uncontrolled cardiac angina or symptomatic congestive heart failure
* Organ transplant (allograft) recipient

Primary outcomes:
measure: The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
timeFrame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
Secondary outcomes:
measure: The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
timeFrame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12
measure: CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
timeFrame: Immunological samples taken at study appointments during the 12 week protocol schedule
measure: Treg Cell:Tcon Cell Ratio
timeFrame: Immunological samples taken at study appointments during the 12 week protocol schedule
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: John Koreth, MBBS, D.Phil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.