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

• 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: Dana-Farber Cancer Institute
• Collaborators: National Cancer Institute (NCI); Prometheus Laboratories
• Information provided by (Responsible Party): John Koreth, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: June 2, 2011
• First Posted Date: June 3, 2011
• Results First Submitted Date: December 18, 2014
• Results First Posted Date: January 15, 2015
• Last Update Posted Date: March 6, 2023
• Study Start Date: July 2011
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 7, 2015)

Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD [ Time Frame: Baseline, 6 weeks, and 12 weeks ]

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.

• Original Primary Outcome Measures (submitted: June 2, 2011): To determine the overall response rate of low-dose daily SC IL-2 in steroid-refractory cGVHD [ Time Frame: 3 years ]

Current Secondary Outcome Measures (submitted: January 7, 2015)

• Toxicity of 12-week Course of Low-dose SC IL-2 Therapy [ Time Frame: 12 weeks ]
  Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course
• Prednisone Taper With IL-2 Therapy [ Time Frame: End of treatment after 16 weeks or most recent follow-up date for patients on extended ]
  Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.
• Overall Survival and Progression-free Survival [ Time Frame: 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.
• Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts [ Time Frame: 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.
• Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: June 2, 2011)

• To determine toxicity of low-dose SC IL-2 therapy [ Time Frame: 3 years ]
• To determine ongoing prednisone use with IL-2 therapy [ Time Frame: 3 years ]
• To assess overall survival, progression-free survival, non-relapse mortality and relapse at 1 year after start of IL-2 [ Time Frame: 3 years ]
• To assess the immunologic effects of low-dose daily SC IL-2 [ Time Frame: 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
• Official Title: A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease
• Brief Summary: Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD.

Detailed Description

You will give yourself or be given IL-2 daily through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 12 weeks. You will then have 4 weeks off of IL-2. During the first 6 weeks of IL-2, you will continue to take steroids without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.

While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system.

You will have clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks. You will also have immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.

You will be on the study for about 16 weeks. You may continue on study treatment for longer if you experience a clinical benefit.

• Study Type: Interventional
• Study Phase: Phase 2
• 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

Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus

Other Name: IL-2

Study Arms

Experimental: Interleukin-2

Each study participant will receive daily subcutaneous IL-2 (1 x 106 IU/m2/day) for self-administration for 12 weeks, followed by a 4-week hiatus. IL-2 will be typically administered on an outpatient basis. After completing the 16 week study (12 weeks of IL-2 study treatment and a mandatory 4 weeks off-IL-2), patients experiencing clinical benefit (complete or partial response; as well as minor response not meeting NIH criteria for partial response) with an acceptable toxicity profile will be permitted to continue extended-duration treatment indefinitely at the discretion of the treating physician.

Intervention: Drug: Interleukin-2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 7, 2015): 35
• Original Estimated Enrollment (submitted: June 2, 2011): 31
• Estimated Study Completion Date: December 2024
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Recipient of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
• Steroid refractory cGVHD with systemic therapy onset within the prior 6 months
• No more than 2 prior lines of cGVHD therapy
• Estimated life expectancy > 3 months
• Adequate organ function

Exclusion Criteria:

• Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
• Concurrent use of calcineurin-inhibitors plus sirolimus
• History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
• Active malignant relapse
• Active uncontrolled infection
• Uncontrolled cardiac angina or symptomatic congestive heart failure
• Organ transplant (allograft) recipient
• HIV-positive on combination antiretroviral therapy
• Active hepatitis B or C
• Pregnant or breast-feeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01366092
• Other Study ID Numbers: 11-149; P01CA142106 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: John Koreth, MD, Dana-Farber Cancer Institute
• Original Responsible Party: John Koreth, MBBS, DPhil, Dana-Farber Cancer Institute
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current

Collaborators

• National Cancer Institute (NCI)
• Prometheus Laboratories

Investigators

• Principal Investigator: John Koreth, MBBS, DPhil; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: March 2023