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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Prometheus Laboratories
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01366092
First received: June 2, 2011
Last updated: January 7, 2015
Last verified: January 2015
  Purpose

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 Intervention Phase
Chronic Graft-versus-host Disease
Drug: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD [ Time Frame: Baseline, 6 weeks, and 12 weeks ] [ Designated as safety issue: No ]
    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:
  • Toxicity of 12-week Course of Low-dose SC IL-2 Therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: July 2011
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Interleukin-2 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01366092

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02214
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Dana-Farber Cancer Institute
Prometheus Laboratories
Investigators
Principal Investigator: John Koreth, MBBS, DPhil Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01366092     History of Changes
Other Study ID Numbers: 11-149, P01CA142106
Study First Received: June 2, 2011
Results First Received: December 18, 2014
Last Updated: January 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
stem cell transplant
GVHD
bone marrow transplant
cord blood transplant
regulatory T cell
interleukin

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Interleukin-2
Analgesics
Analgesics, Non-Narcotic
Antineoplastic Agents
Central Nervous System Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 19, 2015