UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease (GVHD)
Title of the study (Brief title)	A Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease (GVHD)
Region	Japan

Condition
Condition	Chronic GVHD refractory to systemic steroid therapy
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety and efficacy of low dose IL-2 therapy in patients with steroid refractory chronic GVHD
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	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)
Key secondary outcomes	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

In outcomes field, the entry of just a few words such as "safety" or "efficiency" will not be accepted. Specify the name of outcome measures, including the time when you plan to measure. Usually, only one primary outcome is accepted. Write the other outcomes in "secondary outcomes" field.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	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 weeks. Patients with safe toxicity profile and clinical benefit could continue to receive subcutaneous IL-2 for the additional 36 weeks.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

In interventions field, include the details of interventions, such as duration, amount, and frequency. If the intervention includes prescription or use of medical devices, duration is required.

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key 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
Key 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
Target sample size	18

Research contact person
Name of lead principal investigator	Ken-ichi Matsuoka
Organization	Okayama University Hospital
Division name	Department of Hematology and Oncology
Address	2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
TEL	086-235-7227
Email	k-matsu@md.okayama-u.ac.jp

Public contact
Name of contact person	Ken-ichi Matsuoka
Organization	Okayama University Hospital
Division name	Department of Hematology and Oncology
Address	2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
TEL	086-235-7227
Homepage URL	http://www.ldil2.jp
Email	k-matsu@md.okayama-u.ac.jp

Sponsor
Institute	Okayama University Hospital
Institute
Department

Sponsor means an organization that is responsible for plan, deployment and report of the research including funding management. It doesn't mean funding agency". Therefore, all clinical trial should have the one.

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	岡山大学病院（岡山県）、札幌医科大学付属病院（北海道）、東京都立駒込病院（東京都）、千葉大学医学部附属病院（千葉県）、名古屋大学医学部附属病院（愛知県）、関西医科大学附属病院（大阪府）、国立病院機構南岡山医療センター（岡山県）、愛媛県立中央病院（愛媛県）、九州大学病院（福岡県）

Other administrative information
Date of disclosure of the study information	2016 Year 05 Month 09 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2015 Year 03 Month 03 Day
Anticipated trial start date	2015 Year 08 Month 11 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 05 Month 09 Day
Last modified on	2016 Year 05 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025643