Clinical Trial: Extracorporeal Photopheresis and Low Dose Aldesleukin in Treating Patients With Steroid Refractory Chronic Graft-Versus-Host Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Trial of Extracorporeal Photopheresis (ECP) Plus Low Dose IL-2 for Treatment of Steroid Refractory Chronic Graft-versus-Host Disease (cGVHD)

Brief Summary: This phase II trial studies efficacy of extracorporeal photopheresis and low dose aldesleukin (interleukin-2) in treating patients with chronic graft-versus-host disease (cGVHD) that does not respond to upfront treatment with steroids. In graft-vs-host disease, patients have a small quantity of a white blood cell called T regulatory cells or T-reg cells that helps to control the immune system. Extracorporeal photopheresis is a procedure where patient's blood is removed and treated with ultraviolet light and drugs that become active when exposed to light. The treated blood is then returned to the patient and may be effective in increasing T-reg cells in patients with cGVHD. Aldesleukin increases the activity and growth of white blood cells, and it has shown to enhance T-reg cells in patients with cGVHD and may be effective improving GVHD symptoms.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the anti-cGVHD activity of extracorporeal photopheresis (ECP) when combined with low dose IL-2 (interleukin 2) (aldesleukin), in patients with steroid refractory cGVHD, as assessed by overall cGVHD response rate (complete response [CR]+partial response [PR]+stable disease [SD]).

SECONDARY OBJECTIVES:

I. Characterize and evaluate toxicities, including type, frequency, severity, attribution, time course and duration.

II. Estimate overall and failure-free survival, non-relapse mortality (NRM) and relapse, through 1 year after initiation of treatment.

III. Characterize chronic GVHD Symptom Scale scores -self-report (with assistance from register nurses [RNs] and medical doctors [MDs]).

IV. Assess the immunologic effects of low-dose daily subcutaneous (SC) IL-2 + ECP.

V. Correlate clinical endpoints of response with ECP performance parameters.

OUTLINE:

Patients receive aldesleukin subcutaneously (SC) daily for 12 weeks. Patients also undergo ECP twice weekly on weeks 1-4 and then receive 2 ECP treatments every 2 weeks on weeks 5-12. Patients responding to upfront therapy with aldesleukin and ECP have the option to continue combination therapy per the discretion of the treating physician until clinical benefit is maintained or toxicities develop.

After completion of study treatment, patients are followed up periodically.


Sponsor: City of Hope Medical Center

Current Primary Outcome: Overall response (CR+ PR+SD) based on the National Institutes of Health cGVHD consensus criteria [ Time Frame: Up to 4 weeks after the end of treatment ]

The overall response rate (CR+PR) will be calculated as the percent of evaluable patients; exact 95% confidence intervals will be calculated for these estimates. Response rates will also be evaluated based on number and type of prior therapy(ies). Time to response and duration of response will be estimated using the product-limit method of Kaplan and Meier.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in immunologic function [ Time Frame: Baseline to up to 4 weeks after the end of treatment ]

    The following markers will be studied at baseline , 3 week intervals and at end of study to evaluate immunological response to ECP+ IL-2 treatment.

    • Effector memory cells ( CD 45RA-CCR7-/CD62-)
    • Th17 cells
    • Tregs ( CD4+CD25+CD127-)
    • TRECS (T cell receptor excision circles)
    • CD3+ Cells ( T con)17
    • CD 19+( B cell marker )
    • CD3-CD16+CD56+( NK cells)
    • FoxP3 gene methylation status

    Inflammatory Markers:

    • IFN-γ, TNF α
    • IL-2,IL-4,IL-6,IL-8
    • BAFF
    • IL-2 receptor α (IL2R α) and hepatocyte growth factor (HGF) for systemic GVHD
    • Elafin for skin GVHD
    • Regenerating islet-derived 3α (REG3α) for gastrointestinal GVHD
    • Suppression of tumorigenicity 2 (ST2) for steroid-refractoriness
    • CXCL9
    • Micro RNA analysis
    • Plasma banking to be done for microRNA analysis for cGVHD
    • Skin biopsy specimens will be taken at beginning and end of therapy as clinically appropriate.
  • Chronic GVHD symptom score using the GVHD Symptom Scale [ Time Frame: Up to 16 weeks ]
    Self-Reported symptom Scales will be obtained at baseline and weeks 3, 6, 9, 12 and 16.
  • ECP performance parameters will be analyzed based on Median time spent for each ECP session. [ Time Frame: Up to 4 weeks after the end of treatment ]
    Clinical response to therapy will be co-related with ECP performance parameters which will include median time spent on ECP machine, second versus third generation device, and flow.
  • ECP performance parameters will be analyzed based on Flow rates during each ECP session. [ Time Frame: Up to 4 weeks after the end of treatment ]
    Clinical response to therapy will be co-related with ECP performance parameters which will include median time spent on ECP machine, second versus third generation device, and flow.
  • ECP performance parameters will be analyzed based on Outcomes based on use of second or third generation devices. [ Time Frame: Up to 4 weeks after the end of treatment ]
    Clinical response to therapy will be co-related with ECP performance parameters which will include median time spent on ECP machine, second versus third generation device, and flow.
  • Failure-free survival [ Time Frame: From date of first dose of study drug to first documented cGVHD progression (necessitating change of treatment), malignancy relapse or progression or death from any cause, whichever occurs first, assessed up to 4 years ]
  • Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 4 weeks after the end of treatment ]
    Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome. Baseline information (e.g. the extent/type of prior therapy) and demographic information will be presented as well to describe the patients treated in this study.
  • Non-relapse mortality [ Time Frame: From date of first dose of study drug to death from any cause among patients without active disease, assessed up to 4 years ]
  • Overall survival [ Time Frame: From date of first dose of study drug to date of death from any cause, assessed up to 4 years ]
    Overall survival will be estimated using the product-limit method of Kaplan and Meier.


Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: November 23, 2015
Date Started: November 17, 2016
Date Completion: December 2020
Last Updated: March 31, 2017
Last Verified: March 2017