Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid-refractory or Dependent Chronic GVHD (CARE)

Phase II multicenter, Canadian only study - open to 25 subjects. Study open to subjects with steroid-refractory or dependent chronic graft vs host disease.

Series of 6 aphereses and 28 re-infusions over 24 weeks. Primary endpoint is FFS at 24 weeks. Primary objective is to measure the efficacy of CARE (Continuous Alloreactive T-Cell depletion and Regulatory T-cell Expansion)

Study Overview

• Status: Unknown
• Conditions: Chronic GVHD After HCT for Cancer or Immune Disease
• Intervention / Treatment: Other: Autologous peripheral blood mononuclear cells ex vivo depleted for reactive T cells, using TH9402 based photodynamic therapy, in a final formulation of 10% DMSO, 30% autologous plasma in PlasmaLyte.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Hospital Maissoneuve

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: (Main)

• 1. Newly diagnosed chronic GVHD as defined by the National Institutes of Health (NIH) Consensus with no more than 24 weeks of treatment with systemic steroids.

AND 2. Chronic GVHD must be refractory or dependent to standard therapy, defined as (one of the following):

• Progression on prednisone 7 mg/kg/week for 2 weeks, or
• Stable disease on ≥ 3.5 mg/kg/week of prednisone for 4-8 weeks, or
• Inability to taper prednisone below 3.5 mg/kg/week.

Exclusion Criteria: (Main)

• 1. Persistent, recurrent or late-onset acute GVHD, without signs of chronic GVHD.

OR 2. Overlap GVHD syndrome with uncontrolled features of previously diagnosed acute GVHD.

OR 3. Treatment with more than two systemic non-steroidal immunosuppressants within 4 weeks prior to enrollment.

OR 4. Time from allogeneic transplantation > 2 years. OR 5. Lymphocyte count < 0.2 x 109/L on two last consecutive CBCs before inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Open-label phase II study. After signing informed consent, patients will undergo 6 times an apheresis during the 6-month treatment period. These cells will be manufactured into the Rhitol and frozen in aliquots. Then re-infused.	Other: Autologous peripheral blood mononuclear cells ex vivo depleted for reactive T cells, using TH9402 based photodynamic therapy, in a final formulation of 10% DMSO, 30% autologous plasma in PlasmaLyte.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is failure-free survival (FFS) at 24 weeks	24 weeks

Collaborators and Investigators

• Sponsor: daphne brockington

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: July 16, 2015
• First Submitted That Met QC Criteria: August 6, 2015
• First Posted (Estimate): August 11, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Steroid refractory; post stem cell transplantation; dependent chronic
• Additional Relevant MeSH Terms: Immune System Diseases; Pharmaceutical Solutions; Ophthalmic Solutions; Plasma-lyte 148
• Other Study ID Numbers: CNTRP 1401