A Phase II Trial of Low-Dose Interleukin-2 (IL-2) Added to Extra-Corporeal Photopheresis for Steroid-Refractory cGVHD

NCT02340676 | Completed Phase 2 Results DMC

• 1 other identifier: 14-479
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Graft-versus-host-disease

Keywords

chronic graft-versus-host-disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participant With Response at Week 16

  Participants will have their cGVHD evaluated at baseline through Week 16.

  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

  Baseline through Week 16 of the study

• Regulatory T Cell Counts During ECP Plus Low-dose Daily SC IL-2

  Baseline through Week 16 of the study

• Prednisone Use During ECP Plus Low-dose IL-2 From Baseline Through Week 16 of Study

  Baseline through Week 16 of the study

• Overall Survival

  From the start of treatment to 1 Year

• Progression-free Survival

  From the start of treatment to 1 Year

Study Arms (1)

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

Procedure: Extracorporeal Photopheresis (ECP); Drug: Interleukin-2

Interventions

Interleukin-2 DRUG

Participants receive daily IL-2 injections starting Week 8 of study and ending at Week 16

Also known as: IL-2, Proleukin®

ECP plus IL-2

Extracorporeal Photopheresis (ECP) PROCEDURE

Participants receive ECP treatment twice a week for 16 weeks

ECP plus IL-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Prometheus Laboratories: collaborator

Study Sites (1)

Dana-Farber Cancer Insitute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 30936057 DERIVED

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Photopheresis; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. John Koreth, MBBS, DPhil
• Organization: Dana-Farber Cancer Institute

John_Koreth@dfci.harvard.edu

(617) 632-2949

Study Officials

• John Koreth, MBBS,D.Phil

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 7, 2015
• First Posted: January 19, 2015
• Study Start: February 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: September 1, 2025
• Last Updated: February 20, 2026
• Results First Posted: October 18, 2018

Record last verified: 2026-02

Locations

US (1)