Chronic Graft-versus-host-diseasePhase 2NCT02340676
A Phase II Trial of Low-Dose Interleukin-2 (IL-2) Added to Extra-Corporeal Photopheresis for Steroid-Refractory cGVHD
A Phase 2 study testing Extracorporeal Photopheresis (ECP) and Interleukin-2 in people with Chronic Graft-versus-host-disease, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is evaluating a combination of a therapy called Extra-corporeal Photopheresis (ECP) with a drug called Interleukin-2 (IL-2) as a possible treatment for chronic graft-versus-host-disease (GVHD) following allogeneic stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft-versus-host-disease
- What is being tested?
- Extracorporeal Photopheresis (ECP) and Interleukin-2
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Sep 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Recipients of 7-8/8 HLA matched adult donor allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens.
- Participants must have steroid-refractory cGVHD. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D; section 17.4) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms. Patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible.
- Stable dose of corticosteroids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
- Patient age ≥18 years old. Because no dosing or adverse event data are currently available on the use of IL-2 in participants <18 years of age, children are excluded from this study.
Show all 16Show fewer
- Estimated life expectancy greater than 3 months.
- ECOG performance status 0-2 (Appendix A; section 17.1).
- Participants must have adequate organ function as defined below:
- Hepatic: Adequate hepatic function (total bilirubin <2.0 mg/dl-exception permitted in patients with Gilbert's Syndrome; AST (SGOT)/ALT (SGPT) ≤ 2x ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD. For patients with abnormal LFTs as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment. Abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation.
- Renal: Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Pulmonary: FEV1 ≥ 50% or DLCO(Hb) ≥ 40% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD.
- Adequate bone marrow function indicated by ANC>1000/mm3 and platelets>50,000/mm3 without growth factors or transfusions
- Cardiac: No myocardial infarction within 6 months prior to enrollment or NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- The effects of IL-2 on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- Ongoing prednisone requirement >1 mg/kg/day (or equivalent).
- Concurrent use of calcineurin-inhibitors plus sirolimus. Either agent alone is acceptable.
- History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
- Extra-corporeal Photopheresis (ECP) or rituximab therapy within 4 weeks prior to enrollment
Show all 18Show fewer
- Any contraindication to ECP, i.e. contraindication to heparin or 8-MOP.
- Post-transplant exposure to any novel immunosuppressive medication (e.g., alemtuzumab) within 100 days prior to enrollment.
- Donor lymphocyte infusion within 100 days prior to enrollment.
- Active malignant relapse.
- Active uncontrolled infection.
- Inability to comply with IL-2 treatment regimen.
- Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA Class III or IV: Appendix C; section 17.3).
- Organ transplant (allograft) recipient.
- HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic HSCT. In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Individuals with active hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after HSCT.
- Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator.
- Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Insitute
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Trial of Low-Dose Interleukin-2 (IL-2) Added to Extra-Corporeal Photopheresis for Steroid-Refractory Chronic Graft-versus-Host-Disease
This research study is evaluating a combination of a therapy called Extra-corporeal Photopheresis (ECP) with a drug called Interleukin-2 (IL-2) as a possible treatment for chronic graft-versus-host-disease (GVHD) following allogeneic stem cell transplant.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved IL-2 for the treatment of chronic GVHD but it has been approved for metastatic renal cell carcinoma (MCC) and metastatic melanoma. ECP is a standard of care treatment for chronic GVHD that has not responded to steroids.
Chronic GVHD is a medical condition that may occur after receiving bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease.
Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigstors are looking to assess whether the combination of IL-2 and ECP therapy helps control chronic GVHD by stopping the donor's immune system from 'rejecting' the participant's body.
Participants will receive standard-of-care ECP treatment two times a week for 16 weeks. Each treatment will last approximately 2-3 hours. Starting after Week 8 of the ECP treatments, participants will give themselves or be given IL-2 through an injection under their skin. Participants will do this once every day for 8 weeks until the end of the 16-week ECP treatment. If a participant's GVHD worsens during the initial 8 weeks of ECP treatment, he or she has the option of starting IL-2 early.
If a participant's chronic GVHD improves at the end of the 16-week study duration, he or she may have the option of continuing the combination therapy of ECP and IL-2. Extended duration therapy is twice weekly ECP treatments plus daily IL-2 starting at the end of week 16. Participants may also have the option of continuing ECP treatments without IL-2 after the end of Week 16. If this is the case, participants will only be followed for one year from the start of therapy and will not have required study visits or tests.
- Conditions
- Chronic Graft-versus-host-disease
- Being tested
- Extracorporeal Photopheresis (ECP), Interleukin-2
- Keywords
- chronic graft-versus-host-disease
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracorporeal Photopheresis (ECP)Procedure or surgery
Participants receive ECP treatment twice a week for 16 weeks
Interleukin-2Drug
Also called IL-2, Proleukin®
Participants receive daily IL-2 injections starting Week 8 of study and ending at Week 16
| Study group | Role | What they receive |
|---|---|---|
| ECP plus IL-2 | Experimental | * Extracorporeal Photopheresis (ECP) standard-of-care
* Daily subcutaneous (SC) interleukin-2 (IL-2) (Proleukin®) during predetermined weeks of treatment cycle Receives: Procedure: Extracorporeal Photopheresis (ECP); Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participant With Response at Week 16
Participants will have their cGVHD evaluated at baseline through Week 16.
Measured: Baseline through Week 16 of the study
Secondary outcomes (7)
Number of Grade 3 or Higher Toxicities Related to ECP Plus Low-dose SC IL-2 Therapy
All Grade 3 or higher toxicities related to ECP plus low-dose SC IL-2 therapy have been reported.
Measured: Baseline through Week 16 of the study
Regulatory T Cell Counts During ECP Plus Low-dose Daily SC IL-2
Assays will be conducted to detect Change in Regulatory T cell counts during ECP plus low-dose daily SC IL-2
Measured: Baseline through Week 16 of the study
Prednisone Use During ECP Plus Low-dose IL-2 From Baseline Through Week 16 of Study
Prednisone use was assessed during ECP plus low-dose IL-2 treatment at baseline through Week 16 of study.
Measured: Baseline through Week 16 of the study
Overall Survival
Overall survival From the start of treatment to 1 Year was assessed
Measured: From the start of treatment to 1 Year
Progression-free Survival
One year overall survival was analyzed
Measured: From the start of treatment to 1 Year
Non-relapse Mortality
Participants one year cumulative incidence of Non-relapse mortality was assessed.
Measured: From the start of treatment to 1 Year
Relapse at 1 Year
Relapse at 1 year was assessed
Measured: From the start of treatment to 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2015 (estimated)
- Study startFeb 2015
- Primary completionAug 2017
- Study completionSep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Graft-versus-host-diseaseStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Prometheus Laboratories
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS,D.Phil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02340676
- Sponsor's protocol ID
- 14-479
- Status last verified
- Feb 2026
- First submitted
- 7 Jan 2015
- Last updated
- 20 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Belizaire R, Kim HT, Poryanda SJ, Mirkovic NV, Hipolito E, Savage WJ, Reynolds CG, Fields MJ, Whangbo J, Kubo T, Nikiforow S, Alyea EP, Armand P, Cutler CS, Ho VT, Blazar BR, Antin JH, Ritz J, Soiffer RJ, Koreth J. Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019 Apr 9;3(7):969-979. doi: 10.1182/bloodadvances.2018029124.
PubMed 30936057
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Low-Dose Interleukin-2 (IL-2) Added to Extra-Corporeal Photopheresis for Steroid-Refractory Chronic Graft-versus-Host-Disease
- ClinicalTrials.gov ID
- NCT02340676
- Acronym / sponsor ID
- 14-479
- Conditions
- Chronic Graft-versus-host-disease
- Keywords
- chronic graft-versus-host-disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Prometheus Laboratories
- Study start
- Feb 2015
- Primary completion
- Aug 2017 (actual)
- Study completion
- Sep 2025 (actual)
- First posted
- 19 Jan 2015 (estimated)
- Results
- Posted 18 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is evaluating a combination of a therapy called Extra-corporeal Photopheresis (ECP) with a drug called Interleukin-2 (IL-2) as a possible treatment for chronic graft-versus-host-disease (GVHD) following allogeneic stem cell transplant.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved IL-2 for the treatment of chronic GVHD but it has been approved for metastatic renal cell carcinoma (MCC) and metastatic melanoma. ECP is a standard of care treatment for chronic GVHD that has not responded to steroids.
Chronic GVHD is a medical condition that may occur after receiving bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease.
Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigstors are looking to assess whether the combination of IL-2 and ECP therapy helps control chronic GVHD by stopping the donor's immune system from 'rejecting' the participant's body.
Participants will receive standard-of-care ECP treatment two times a week for 16 weeks. Each treatment will last approximately 2-3 hours. Starting after Week 8 of the ECP treatments, participants will give themselves or be given IL-2 through an injection under their skin. Participants will do this once every day for 8 weeks until the end of the 16-week ECP treatment. If a participant's GVHD worsens during the initial 8 weeks of ECP treatment, he or she has the option of starting IL-2 early.
If a participant's chronic GVHD improves at the end of the 16-week study duration, he or she may have the option of continuing the combination therapy of ECP and IL-2. Extended duration therapy is twice weekly ECP treatments plus daily IL-2 starting at the end of week 16. Participants may also have the option of continuing ECP treatments without IL-2 after the end of Week 16. If this is the case, participants will only be followed for one year from the start of therapy and will not have required study visits or tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ECP plus IL-2 | Experimental | Procedure: Extracorporeal Photopheresis (ECP), Drug: Interleukin-2* Extracorporeal Photopheresis (ECP) standard-of-care * Daily subcutaneous (SC) interleukin-2 (IL-2) (Proleukin®) during predetermined weeks of treatment cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants must meet the following criteria on screening examination to be eligible to participate in the study:
- Recipients of 7-8/8 HLA matched adult donor allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens.
- Participants must have steroid-refractory cGVHD. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D; section 17.4) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms. Patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible.
- Stable dose of corticosteroids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
Key exclusion criteria (18 listed)
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- Ongoing prednisone requirement >1 mg/kg/day (or equivalent).
- Concurrent use of calcineurin-inhibitors plus sirolimus. Either agent alone is acceptable.
- History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extracorporeal Photopheresis (ECP)Participants receive ECP treatment twice a week for 16 weeks | Procedure or surgery | ECP plus IL-2 |
| Interleukin-2Also: IL-2, Proleukin®Participants receive daily IL-2 injections starting Week 8 of study and ending at Week 16 | Drug | ECP plus IL-2 |
Primary outcome
Percentage of Participant With Response at Week 16
Time frame: Baseline through Week 16 of the study
Participants will have their cGVHD evaluated at baseline through Week 16.
7 secondary outcomes
Number of Grade 3 or Higher Toxicities Related to ECP Plus Low-dose SC IL-2 Therapy
Time frame: Baseline through Week 16 of the study
Regulatory T Cell Counts During ECP Plus Low-dose Daily SC IL-2
Time frame: Baseline through Week 16 of the study
Prednisone Use During ECP Plus Low-dose IL-2 From Baseline Through Week 16 of Study
Time frame: Baseline through Week 16 of the study
Overall Survival
Time frame: From the start of treatment to 1 Year
Progression-free Survival
Time frame: From the start of treatment to 1 Year
Non-relapse Mortality
Time frame: From the start of treatment to 1 Year
Relapse at 1 Year
Time frame: From the start of treatment to 1 Year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30936057Belizaire R, Kim HT, Poryanda SJ, Mirkovic NV, Hipolito E, Savage WJ, Reynolds CG, Fields MJ, Whangbo J, Kubo T, Nikiforow S, Alyea EP, Armand P, Cutler CS, Ho VT, Blazar BR, Antin JH, Ritz J, Soiffer RJ, Koreth J. Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019 Apr 9;3(7):969-979. doi: 10.1182/bloodadvances.2018029124.
Related trials for Chronic Graft-versus-host-disease
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruiting
Feasibility of a Robot-Guided Active Play Intervention for Children With Cerebral Palsy
Cerebral Palsy
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Koreth, MBBS,D.Phil principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Extracorporeal Photopheresis (ECP) and Interleukin-2 in people with Chronic Graft-versus-host-disease, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participant With Response at Week 16 (time frame: Baseline through Week 16 of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02340676, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.