Multiple Donor Treg DLI for Severe Refractory Chronic GVHD (TREG2015001)

• ClinicalTrials.gov Identifier: NCT02749084
• Recruitment Status: Recruiting
• First Posted: April 22, 2016
• Last Update Posted: January 18, 2019
• Sponsor: Mario Arpinati
• Collaborator: European Commission
• Information provided by (Responsible Party): Mario Arpinati, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Study Description

Brief Summary:

This is a INTERVENTIONAL TRANSPLANTATION STUDY WITHOUT DRUGS.

The INTERVENTION is represented by the INFUSION of DONOR T REGULATORY CELL-ENRICHED LYMPHOCYTES to PATIENTS suffering from REFRACTORY CHRONIC GVHD after ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.

The study includes a DOSE ESCALATION PHASE followed by a MTD PHASE as detailed in the following chapter.

The primary objective of the dose escalation study will be SAFETY, leading to the definition of the MTD of T reg cells. For the MTD study the primary objective will be the OVERALL RESPONSE RATE at three months after the 3rd Treg infusion.

The study is single center single arm open label and includes a DOSE ESCALATION phase followed by an EXTENDED PHASE with the MAXIMUM TOLERATED DOSE (MTD).

The aim of the study is to assess whether multiple infusions of donor-derived purified T regulatory cells (T reg DLI) in patients with steroid-refractory chronic GVHD is safe and whether it may induce clinical remission of GVHD.

Condition or disease	Intervention/treatment	Phase
Chronic Graft Versus Host Disease	Biological: T reg DLI	Phase 1; Phase 2

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multiple Donor Regulatory T Cell (Treg) Infusions (T Reg DLI) for Severe Refractory Chronic Graft Versus Host Disease (GVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
• Actual Study Start Date: August 3, 2016
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: T reg DLI; This is a INTERVENTIONAL TRANSPLANTATION STUDY WITHOUT DRUGS. The INTERVENTION is represented by the INFUSION of DONOR T REGULATORY CELL-ENRICHED LYMPHOCYTES to PATIENTS suffering from REFRACTORY CHRONIC GVHD after ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION. The study is single center single arm open label and includes a DOSE ESCALATION phase followed by an EXTENDED PHASE with the MAXIMUM TOLERATED DOSE (MTD). During the dose escalation phase each patient will receive three doses of purified donor T reg cells each administered intravenously 1 month apart. Dose levels of purified Tregs will be 5x10e5/kg, 1x10e6/kg and 2x10e6/kg, resulting in three doses of 1.7x10e5/kg, 3.3x10e5/kg and 6.6x10e5/kg, respectively. In the dose escalation study at least 9 patients will be required depending on the occurrence of adverse events during the study). Patients in the MTD study should be about 10, according to Fleming.

Biological: T reg DLI; Purified Treg cells will be obtained from the original HSC donor (T reg DLI). Tregs preparation will start with unstimulated donor leukapheresis from the original stem cell donor. The apheresis product will be provided to the Cell Factory "Calori",Milano, where T reg purification will take place. T reg cells will be PURIFIED utilizing the CliniMACS Plus Systems for depletion of CD8 and CD19 positive cells and enrichment for CD25high cells. Release Criteria of Treg cell preparation will be defined. The product will be infused into the recipient through a venous catheter.; Other Name: T regulatory cell infusion

Outcome Measures

Primary Outcome Measures :

1. OVERALL RESPONSE RATE [ Time Frame: 3 months after last T reg infusion ]

   The response of chronic GVHD to treatment will be assessed per NIH consensus criteria.

   Overall response will be defined as either a complete o partial response.

   Complete Response is defined as resolution of all reversible manifestations related to cGVHD in a specific organ.

   Partial Response will be defined as at least 50% improvement in the scale used to measure disease manifestations related to cGVHD (e.g. a 50% decrease in skin rash from 80% BSA to 40% BSA), in at least one organ or site, without progression in measures at any other organ or site.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Any patient who has undergone allogeneic stem cell transplantation with steroid refractory severe chronic GvHD either occurring post transplant, or induced by donor lymphocyte infusions (DLI) or T-cell add back. The diagnosis of chronic GvHD will based on NIH criteria, 2014 update. Chronic GvHD grading will be performed based on the updated NIH criteria. Severe chronic GVHD will be defined as having SCORE 3 in at least one organ or SCORE 2-3 in the lung.

  • Refractoriness to steroids will be defined based on the following criteria:

    1. use of at least another immunosuppressive medication/strategy besides prophylactic calcineurin inhibitor for previous treatment for cGVHD .
    2. use of prednisone ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) (or equivalent dosing of alternate glucocorticoids) for at least 4 weeks prior to enrollment without complete resolution of signs and symptoms.

exclusion criteria:

• Inability to obtain informed consent.
• Patients with documented active EBV, CMV or fungal infection.
• Patients with active HBV, HCV o HIV infection.
• Patients with a diagnosis of solid tumor within the previous year with the exception of NON melanoma skin cancer.
• Patients with evidence of Residual Disease at their last hematologic evaluation.
• Patients in poor clinical conditions (ECOG 3-4)
• Female patients with confirmed pregnancy

Contacts and Locations

Contacts

Contact: Mario Arpinati, MD; +39051214 ext 4073; mario.arpinati@unibo.it

Contact: Antonella Orlando; +39051214 ext 3792; antonella.orlando@aosp.bo.it

Locations

Italy

University Hospital St. Orsola-Malpighi Polyclinic; Recruiting

Bologna, BO, Italy, 40138

Contact: Mario Arpinati, MD +390512144073 mario.arpinati@unibo.it

Contact: Antonella Orlando +39 0512143792 antonella.orlando@aosp.bo.it

Principal Investigator: Mario Arpinati, MD

Sponsors and Collaborators

Mario Arpinati

European Commission

More Information

• Responsible Party: Mario Arpinati, Dr Mario Arpinati, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• ClinicalTrials.gov Identifier: NCT02749084 History of Changes
• Other Study ID Numbers: 160/2015/O/Sper
• First Posted: April 22, 2016
• Last Update Posted: January 18, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Mario Arpinati, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi:

chronic graft versus host disease; T regulatory cell

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases