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

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ClinicalTrials.gov Identifier: NCT02749084
Recruitment Status : Recruiting
First Posted : April 22, 2016
Last Update Posted : February 2, 2017
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Mario Arpinati, Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

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 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


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




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.




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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) Performed already at least two attempts of treatment with prednisone at at least 0.5 mg/kg for 21 days in the previous 6 months and (2) treated with at least another immunosuppressive medication for 30 days in the previous 6 months and (3) Requiring at least 0.2 mg/kg prednisone for maintaining stable disease or worsening despite 0.2 mg/kg prednisone.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02749084


Contacts
Contact: Mario Arpinati, MD +39051214 ext 4073 mario.arpinati@unibo.it
Contact: Francesca Ulbar, PhD +39051214 ext 3792 francesca.ulbar@yahoo.it

Locations
Italy
University Hospital St. Orsola-Malpighi Polyclinic Recruiting
Bologna, BO, Italy, 40138
Contact: Enrica Sciulli    +390512143799    enrica.sciulli@aosp.bo.it   
Principal Investigator: Mario Arpinati, MD         
Sponsors and Collaborators
Mario Arpinati
European Commission

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    Key Record Dates
Last Update Posted: February 2, 2017
Last Verified: February 2017
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