Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft Versus Host Disease

NCT00529035 | Completed Phase 1 Results DMC

• 1 other identifier: 07-083
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.

Conditions

Graft Versus Host Disease

Keywords

Chronic GVHD; Steroid refractory GVHD; allogeneic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.

  Three dose levels were evaluated to determine the maximally tolerated dose (MTD): Dose level A: 0.3 x 10\^6 IU/m\^2/day Dose level B: 1.0 x 10\^6 IU/m\^2/day Dose level C: 3.0 x 10\^6 IU/m\^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.

  Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy

Secondary Outcomes (3)

• The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.

  Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12

• CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.

  Immunological samples taken at study appointments during the 12 week protocol schedule

• Treg Cell:Tcon Cell Ratio

  Immunological samples taken at study appointments during the 12 week protocol schedule

Study Arms (1)

Interleukin-2

EXPERIMENTAL

Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels: Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d)

Drug: Interleukin-2

Interventions

Interleukin-2 DRUG

Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks.

Also known as: IL-2

Interleukin-2

Eligibility Criteria

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

You may qualify if:

• Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
• Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
• Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months without complete resolution of signs and symptoms.
• Stable dose of corticosteroids for 4 weeks prior to enrollment
• No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment.
• Adequate bone marrow, renal and hepatic function as outlined in the protocol
• years of age or older
• ECOG Performance Status of 0-2

You may not qualify if:

• Ongoing prednisone requirement \> 1mg/kg/day (or equivalent)
• Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
• Concurrent ECP therapy within 4 weeks prior to enrollment
• Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
• Donor lymphocyte infusion within 100 days prior to IL-2 therapy
• Active malignant disease relapse
• Active, uncontrolled infection
• Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
• HIV seropositivity
• Life expectancy \< 3 months
• Pregnancy or lactation
• Inability to comply with IL-2 treatment regimen
• Uncontrolled cardiac angina or symptomatic congestive heart failure
• Organ transplant (allograft) recipient

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Novartis: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.

  PMID: 22129252 RESULT

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: John Koreth, MBBS, D.Phil
• Organization: Dana-Farber Cancer Institute

jkoreth@partners.org

(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 1
• 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: September 11, 2007
• First Posted: September 14, 2007
• Study Start: August 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: May 27, 2020
• Last Updated: July 1, 2020
• Results First Posted: January 29, 2014

Record last verified: 2020-06

Locations

US (1)