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Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01366092
Recruitment Status : Active, not recruiting
First Posted : June 3, 2011
Results First Posted : January 15, 2015
Last Update Posted : March 6, 2023
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Prometheus Laboratories
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Graft-versus-host Disease
Intervention Drug: Interleukin-2
Enrollment 35
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Interleukin-2
Hide Arm/Group Description Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Period Title: Overall Study
Started 35
Completed 31
Not Completed 4
Reason Not Completed
Progressive cGVHD             2
Physician Decision             1
Withdrawal by Subject             1
Arm/Group Title Interleukin-2
Hide Arm/Group Description Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Baseline Participants 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants
51
(22 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
17
  48.6%
Male
18
  51.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 35 participants
35
Time from Allogeneic Stem Cell Transplant  
Median (Full Range)
Unit of measure:  Days
Number Analyzed 35 participants
616
(270 to 2145)
Time from chronic GVHD onsent  
Median (Full Range)
Unit of measure:  Days
Number Analyzed 35 participants
252
(28 to 1880)
Number of cGVHD organ sites  
Median (Full Range)
Unit of measure:  Organs affected by cGVHD
Number Analyzed 35 participants
4
(1 to 7)
Number of concurrent cGVHD therapies  
Median (Full Range)
Unit of measure:  Therapies
Number Analyzed 35 participants
2
(1 to 3)
Baseline Corticosteroid (Prednisone) dose  
Median (Full Range)
Unit of measure:  Milligrams per day
Number Analyzed 35 participants
20
(2.5 to 50)
1.Primary Outcome
Title Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD
Hide Description Participants were evaluated according to the cGVHD NIH Consensus criteria at baseline, 6 weeks, and 12 weeks on study. Per cGVHD NIH Consensus criteria, cGVHD involved organ systems are given a grade 0-3 and an overall cGVHD score, from 0-10, is given. Complete Response is defined as resolution of all reversible manifestations in each organ or site of cGVHD. A partial response is defined as an improvement in measure at least one organ or site, or decrease in global ratings by at least a 2-point change on the 10-point scale, without progression measured at any other organ or site. Non-responders have no change in cGVHD meeting criteria for either partial response or disease progression. Progressive disease is defined as an increase in organ or site scales (1-point change on a 3-point scale) or 2- to 3-point increase on the global cGVHD ratings. Clinical worsening of cGVHD is not synonymous with progressive cGVHD per NIH criteria.
Time Frame Baseline, 6 weeks, and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
33 of 35 patients were evaluable for response criteria. To be evaluable, patients had to receive at least 6 weeks of daily IL-2 and had their disease re-assessed.
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: participants
Overall Partial Response 21
Overall Stable Response 10
Overall cGVHD Progression 2
Skin cGVHD Response 9
Joint/Fascia/Muscle cGVHD Response 4
Liver cGVHD Response 7
Lung cGVHD Response 3
GI tract cGVHD Response 4
2.Secondary Outcome
Title Toxicity of 12-week Course of Low-dose SC IL-2 Therapy
Hide Description Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Grade 2 or higher, related to IL-2, adverse events (AE) were recorded for participants during their 12-week IL-2 treatment course. AE's were evaluated based on the CTCAE version 4.0.
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: Grade 2 or higher related AEs
3
3.Secondary Outcome
Title Prednisone Taper With IL-2 Therapy
Hide Description Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.
Time Frame End of treatment after 16 weeks or most recent follow-up date for patients on extended
Hide Outcome Measure Data
Hide Analysis Population Description
Participant's steroid taper was measured using their steroid dose at the start of therapy and their dose at the end of 16 weeks. For participants who continued on extended duration therapy, their final steroid dose was determined at the time of stopping treatment or, if still ongoing, the last clinic visit at the time of data analysis.
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 33
Mean (Full Range)
Unit of Measure: percent taper
42.8
(0 to 100)
4.Secondary Outcome
Title Overall Survival and Progression-free Survival
Hide Description Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. OS was defined as from the study entry to death from any cause. Patients who were alive or lost to follow-up were censored at the time last seen alive. PFS was defined from the study entry to disease relapse or progression or death from any cause, whichever occurred first.
Time Frame 2 years from start of IL-2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 33
Measure Type: Number
Unit of Measure: probability
Overall Survival 0.91
Progression-Free Survival 0.82
5.Secondary Outcome
Title Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts
Hide Description Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The CD4+CD25+FOXP3+ regulatory T cells (Treg) counts were measured.
Time Frame 16 weeks of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 35
Median (Inter-Quartile Range)
Unit of Measure: cell count/ uL
Baseline regulatory T cell
17.1
(8.6 to 40.6)
Week 4 Treg cell count
137.9
(51.8 to 188)
Week 12 Treg cell count
104.1
(53.9 to 167.1)
6.Secondary Outcome
Title Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio
Hide Description Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The ratio between CD4+CD25+FOXP3+ regulatory T cells (Treg) and CD4 conventional T cell (Tcon) counts were measured.
Time Frame 16 weeks of study follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Interleukin-2
Hide Arm/Group Description:
Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
Overall Number of Participants Analyzed 35
Median (Inter-Quartile Range)
Unit of Measure: ratio
Baseline Treg:Tcon ratio
0.06
(0.05 to 0.13)
Week 2 Treg:Tcon ratio
0.35
(0.26 to 0.48)
Week 12 Treg:Tcon ratio
0.31
(0.27 to 0.39)
Time Frame From first dose of study drug at Week 1 until Week 16 visit.
Adverse Event Reporting Description Participants were evaluated for adverse events at every clinical visit during Weeks 1,2,4,6,8.10,12,16 and every 4 weeks on extended duration therapy. Only serious adverse events and other adverse events that occurred during the 16-week study period are recorded here. Per protocol, only AEs Grade 3 or higher were recorded.
 
Arm/Group Title Interleukin-2
Hide Arm/Group Description Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus
All-Cause Mortality
Interleukin-2
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Interleukin-2
Affected / at Risk (%) # Events
Total   4/35 (11.43%)    
Infections and infestations   
Streptococcus viridans infection † 1 [1]  1/35 (2.86%)  1
Metabolism and nutrition disorders   
Hyperglycemia † 1 [2]  2/35 (5.71%)  3
Respiratory, thoracic and mediastinal disorders   
Pneumothorax † 1 [2]  1/35 (2.86%)  2
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
This event was deemed unrelated to study treatment.
[2]
These events were deemed unrelated to study treatment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Interleukin-2
Affected / at Risk (%) # Events
Total   10/35 (28.57%)    
Blood and lymphatic system disorders   
Platelet count decreased † 1 [1]  1/35 (2.86%)  1
Cardiac disorders   
Hypertension † 1 [2]  2/35 (5.71%)  3
General disorders   
Fatigue † 1 [3]  1/35 (2.86%)  1
Flu-like symptoms † 1 [4]  1/35 (2.86%)  1
Metabolism and nutrition disorders   
Hyperglycemia † 1 [2]  2/35 (5.71%)  2
Hypokalemia † 1 [2]  1/35 (2.86%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia † 1 [2]  1/35 (2.86%)  4
Nervous system disorders   
Peripheral Motor Neuropathy † 1 [2]  1/35 (2.86%)  1
Vascular disorders   
Thromoembolic Event † 1 [2]  2/35 (5.71%)  2
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
This event was deemed possibly related to study treatment
[2]
This event was deemed unrelated to study therapy
[3]
This event was deemed probably related to study treatment
[4]
This event was deemed related to study treatment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John Koreth, MBBS, DPhil
Organization: Dana-Farber Cancer Institute
Phone: 617-632-2949
EMail: JKoreth@partners.org
Layout table for additonal information
Responsible Party: John Koreth, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01366092    
Other Study ID Numbers: 11-149
P01CA142106 ( U.S. NIH Grant/Contract )
First Submitted: June 2, 2011
First Posted: June 3, 2011
Results First Submitted: December 18, 2014
Results First Posted: January 15, 2015
Last Update Posted: March 6, 2023