UMIN-CTR Clinical Trial

Public title

A Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease (GVHD)

Acronym

A Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease (GVHD)

Scientific Title

A Phase I/IIa Study of Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease (GVHD)

Scientific Title:Acronym

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

Chronic GVHD refractory to systemic steroid therapy

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Ken-ichi Matsuoka

Organization

Okayama University Hospital

Division name

Department of Hematology and Oncology

Zip code

Address

2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

TEL

086-235-7227

Email

k-matsu@md.okayama-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Ken-ichi Matsuoka

Organization

Okayama University Hospital

Division name

Department of Hematology and Oncology

Zip code

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

Institute

Okayama University Hospital

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2016

Year

05

Month

09

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2015

Year

03

Month

03

Day

Date of IRB

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

Other related information

Registered date

2016

Year

05

Month

09

Day

Last modified on

2016

Year

05

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000025643