Clinical Trial: Multiple Donor Treg DLI for Severe Refractory Chronic GVHD
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
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 Trans
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.
Detailed Summary:
The procedure under study is the infusion of patients with chronic GVHD with purified Treg cells obtained from the original HSC donor (T reg DLI).
T reg cells are PURIFIED utilizing the CliniMACS Plus Systems for depletion of CD8 and CD19 positive cells and enrichment for CD25high expressing. Treg purification will be performed according to GMP procedure by using the clinical grade CLINI-MACS® device. The protocol is detailed in chapter 3.5
The entire manufacturing process including cell harvesting, transport and Treg purification has been validated.
The feasibility of the selection of nTreg from human peripheral blood using the CliniMACS® System has been previously documented. In these studies, CD8+ and CD19+ cells were undetectable in the final blood products. Final content of CD4+CD25+CD127lo-expressing cells was in mean 79% (range 52-82%) with the improved CD25 enrichment procedure. This protocol has also been validated by two partner Centres in the Treg GENERATION CONSORTIUM, Liège and Boston, with results that meet the release criteria for infusion. These purification procedures provided between 0.98 and 2.93x10e6 Treg per kg. It is noteworthy that the degree of purity in terms of CD4+CD25+CD127- cells ranged between 72.80% and 93.90%.
According to the "Reflection paper on classification of advanced therapy medicinal therapy", published by the Committee for Advanced Therapies (CAT) of the European Medicine Agency on June 20th 2014 [EMA/CAT/600280/2010 Rev.1 lines 118-131] the Treg DLI SHOULD NOT BE CONSIDERED CELL THERAPY MEDICINAL PRODUCTS. Indeed somatic cell therapy medicinal product means a biological medicinal product which fulfils BOTH following two characteristics: (a) contains or consis
Sponsor: Mario Arpinati
Current Primary Outcome: 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.
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
Dates:
Date Received: April 20, 2016
Date Started: August 3, 2016
Date Completion: March 2022
Last Updated: February 1, 2017
Last Verified: February 2017
