Chronic GVHD refractory to systemic steroid therapy
Conditions
Interventions
Patients will receive subcutaneous IL-2 at three dose levels (A: 3x10*4 units/m2/day, B: 1x10*5 units/m2/day, C: 3x10*5 units/m2/day) , daily for the first 4 weeks and 3 times a week for the next 8 we
Sponsors
Okayama University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens 2) Patients must be at least 180 days from the allogeneic stem cell transplantation 3) Patients must have steroid refractory chronic GVHD*. * Prednisolone of 1.0mg/kg/day for 2 weeks, 0.5mg/kg/day for 4 weeks, or 1.0mg/kg/every other day for 4 weeks without complete resolution of signs and symptoms 4) Stable dose of corticosteroids for 2 weeks prior to enrollment 5) No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment 6) Adequate marrow and organ function listed below 1. Absolute neutrophil count (ANC) > 1000 /mm3 2. Platelet count > 50,000 /mm3 3. Absolute lymphocyte count > 400 /mm3 4. AST < 2x ULN 5. Total bilirubin < 2.0 mg/dl 6. Serum creatinine < 2x ULN 7) Patient age >=18 years 8) Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment 9) Written informed consent from all patients
Exclusion criteria
Exclusion criteria: 1) Ongoing prednisone requirement >= 1 mg/kg/day 2) Post-transplant exposure to immunosuppressive medication (TNF-alfa inhibitor, bortezomib, anti-CD20 monoclonal antibody or imatinib) for treatment of chronic GVHD within 2 weeks prior to enrollment 3) Post-transplant exposure to investigational immunosuppressive medication (Extracorporeal photopheresis, Ultraviolet therapy, tamibarotene) within 4 weeks prior to enrollment 4) Exposure to medication (Antithymocyte globulin, Anti- CD52, CD3, CCR4, CD25, CD30, PD-1, PD-L1, CTLA4, alpha-Integrin antibody, CTLA4-Ig or any other antibodies that potentially affect regulatory T cells) within 180 days prior to enrollment 5) Active malignant disease relapse 6) Active, uncontrolled infection 7) Active infection with hepatitis B virus or hepatitis C virus 8) Life expectancy <3 months 9) Pregnancy or lactation 10) Inability to comply with IL-2 treatment regimen 11) Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA Class III or IV) 12) Organ transplant (allograft) recipient 13) HLA >=2 locus mismatches transplantation (except for cord blood transplantation) 14) Unstable cardiac angina, cardiac infarction, deep vein thrombosis or cerebral infarction (CTCAE Grade>=3) 15) Anticoagulant therapy 16) Severe Thrombotic microangiopathy 17) Hematological malignancy expressing CD25 (IL-2 receptor) 18) Intolerance or hypersensitivity to any biological products 19) Patients judged inappropriate for this study by attending physicians
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: To determine the Maximum Tolerated Dose Level (MTD) of a 4 week course of IL-2 in patients with chronic GVHD Phase IIa: To evaluate the 3-month Failure Free Survival (FFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety profiles of IL-2 administration during 12-week and subsequent extended study period 2. Clinical response based on NIH consensus criteria and steroid-dose reduction 3. Explanatory analysis of immune response in terms of increase in regulatory T cells | — |
Countries
Japan
Contacts
Public ContactKen-ichi Matsuoka
Okayama University Hospital Department of Hematology and Oncology
Outcome results
None listed