Trial Outcomes & Findings for Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease (NCT NCT01366092)

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Baseline, 6 weeks, and 12 weeks

Results posted on

2025-09-11

Participant Flow

Participant milestones

Participant milestones
Measure	Interleukin-2 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 Study STARTED	35
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Interleukin-2 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 Study Progressive cGVHD	2
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interleukin-2 n=35 Participants 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
Age, Continuous	51 years n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants
Time from Allogeneic Stem Cell Transplant	616 days n=5 Participants
Time from chronic GVHD onsent	252 days n=5 Participants
Number of cGVHD organ sites	4 organs affected by cGVHD n=5 Participants
Number of concurrent cGVHD therapies	2 therapies n=5 Participants
Baseline Corticosteroid (Prednisone) dose	20 milligrams per day n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6 weeks, and 12 weeks

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Interleukin-2 n=33 Participants 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 Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Overall Partial Response	21 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Overall Stable Response	10 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Overall cGVHD Progression	2 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Skin cGVHD Response	9 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Joint/Fascia/Muscle cGVHD Response	4 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Liver cGVHD Response	7 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD Lung cGVHD Response	3 participants
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD GI tract cGVHD Response	4 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: 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.

Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course

Outcome measures

Outcome measures
Measure	Interleukin-2 n=35 Participants 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
Toxicity of 12-week Course of Low-dose SC IL-2 Therapy	3 Grade 2 or higher related AEs

SECONDARY outcome

Timeframe: End of treatment after 16 weeks or most recent follow-up date for patients on extended

Population: 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.

Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.

Outcome measures

Outcome measures
Measure	Interleukin-2 n=33 Participants 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
Prednisone Taper With IL-2 Therapy	42.8 percent taper Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 2 years from start of IL-2

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.

Outcome measures

Outcome measures
Measure	Interleukin-2 n=33 Participants 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 Survival and Progression-free Survival Overall Survival	0.91 probability
Overall Survival and Progression-free Survival Progression-Free Survival	0.82 probability

SECONDARY outcome

Timeframe: 16 weeks of study follow-up

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.

Outcome measures

Outcome measures
Measure	Interleukin-2 n=35 Participants 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
Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts Baseline regulatory T cell	17.1 cell count/ uL Interval 8.6 to 40.6
Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts Week 4 Treg cell count	137.9 cell count/ uL Interval 51.8 to 188.0
Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts Week 12 Treg cell count	104.1 cell count/ uL Interval 53.9 to 167.1

SECONDARY outcome

Timeframe: 16 weeks of study follow-up

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.

Outcome measures

Outcome measures
Measure	Interleukin-2 n=35 Participants 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
Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio Baseline Treg:Tcon ratio	0.06 ratio Interval 0.05 to 0.13
Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio Week 2 Treg:Tcon ratio	0.35 ratio Interval 0.26 to 0.48
Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio Week 12 Treg:Tcon ratio	0.31 ratio Interval 0.27 to 0.39

Adverse Events

Interleukin-2

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Interleukin-2 n=35 participants at risk 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
Metabolism and nutrition disorders Hyperglycemia	5.7% 2/35 • Number of events 3 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.9% 1/35 • Number of events 2 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Infections and infestations Streptococcus viridans infection	2.9% 1/35 • Number of events 1 • From first dose of study drug at Week 1 until Week 16 visit. 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.

Other adverse events

Other adverse events
Measure	Interleukin-2 n=35 participants at risk 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
Blood and lymphatic system disorders Platelet count decreased	2.9% 1/35 • Number of events 1 • From first dose of study drug at Week 1 until Week 16 visit. 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.
General disorders Fatigue	2.9% 1/35 • Number of events 1 • From first dose of study drug at Week 1 until Week 16 visit. 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.
General disorders Flu-like symptoms	2.9% 1/35 • Number of events 1 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Cardiac disorders Hypertension	5.7% 2/35 • Number of events 3 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Metabolism and nutrition disorders Hyperglycemia	5.7% 2/35 • Number of events 2 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Metabolism and nutrition disorders Hypokalemia	2.9% 1/35 • Number of events 2 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Nervous system disorders Peripheral Motor Neuropathy	2.9% 1/35 • Number of events 1 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/35 • Number of events 4 • From first dose of study drug at Week 1 until Week 16 visit. 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.
Vascular disorders Thromoembolic Event	5.7% 2/35 • Number of events 2 • From first dose of study drug at Week 1 until Week 16 visit. 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.

Additional Information

John Koreth, MBBS, DPhil

Dana-Farber Cancer Institute

Phone: 617-632-2949

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place