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

Study Overview
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Brief Summary
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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)

Official Title
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Continuous Alloreactive T Cell Depletion and Regulatory T Cell Expansion for the Treatment of Steroid-refractory or Dependent Chronic GVHD

Conditions
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Chronic GVHD After HCT for Cancer or Immune Disease

Intervention / Treatment
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* 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.


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>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.<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post stem cell transplantation, Steroid refractory, dependent chronic