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

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.

Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host Disease Drug: Interleukin-2 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease
Study Start Date : July 2011
Actual Primary Completion Date : October 2014
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
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.
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01366092

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United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02214
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Prometheus Laboratories
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Principal Investigator: John Koreth, MBBS, DPhil Dana-Farber Cancer Institute
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Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01366092    
Other Study ID Numbers: 11-149
P01CA142106 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2011    Key Record Dates
Results First Posted: January 15, 2015
Last Update Posted: March 6, 2023
Last Verified: March 2023
Keywords provided by John Koreth, MD, Dana-Farber Cancer Institute:
stem cell transplant
bone marrow transplant
cord blood transplant
regulatory T cell
Additional relevant MeSH terms:
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Bronchiolitis Obliterans Syndrome
Graft vs Host Disease
Immune System Diseases
Organizing Pneumonia
Bronchiolitis Obliterans
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs