Clinical trial NCT03887156: Evaluation of a Donor Testing Kit for the Prediction of AGVHD in Patient Receiving a Peripheral Blood Stem Cell Allograft
Official title: Evaluation of a Donor Testing Kit for the Prediction of Acute GVHD in Patient Receiving a Peripheral Blood Stem Cells Allograft- Predictor 2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Acute Myeloid Leukemia in Remission
Lymphoma in Remission
Non-progressive Myeloproliferative Syndrome
Myelodysplasia With Stable Blasts is Cell Number and < 10% of Blastocysts
Acute Leukemia Biphenotypic in Remission
Acute Lymphoblastic Leukemia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: SATT
name: SNC Graft Versus Host Disease
name: Imagine Institute
name: Axonal-Biostatem
name: CERBA laboratory
First posted: 2019-03-22
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The aim is to validate an in vitro diagnosis medical device to predict grade II to IV aGVHD after a cell graft

Detailed description: Acute Graft Versus Host Disease (aGVHD) is the most frequent complication in allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). It affects up to 50% patients, among whom 15% to 25% develop severe forms, often lethal, yet impossible to predict even for donors with a Human Leukocyte Antigene (HLA) 10/10 compatibility. Global Overall Survival (OS) after transplantation is 40% to 60% only due to post transplant severe complications. There is a major medical need for a technology that would predict the risk of aGVHD and would allow the selection of a favourable donor among multiple Human Leukocyte Antigene (HLA)10/10 compatible donors.

MT. Rubio and M. Bouillié at Pr Olivier Hermine's lab previously reported that enhanced early post-transplant invariant Natural Killer T (iNKT) cells reconstitution from donor cells was correlated to reduced risk of aGVHD, without impairment of the Graft Versus Leukemia (GVL) effect. They subsequently demonstrated that the expansion of donors CD4neg invariant Natural Killer T (iNKT) cells subpopulation was predictive of a reduced risk of aGVHD, and developed a method for predicting this risk based on the expansion factor of CD4neg invariant Natural Killer T (iNKT) cells in the peripheral blood stem cell (PBSC) graft. This invariant Natural Killer T (iNKT) cells functional test reaches its optimal predictive capacity with 94% sensitivity and 100% specificity in allo-HSCT performed with Human Leukocyte Antigene (HLA) 10/10 matched peripheral blood stem cell (PBSC) grafts for non-progressive hematological malignant diseases, in complete response, which represent the majority of the indications of allogeneic HSCT. Similar predictive value was also observed when the test was performed from donor's peripheral blood before G-CSF mobilization. It was not associated with an increased risk of relapse. This test could therefore allow to easily selecting the best donor if different siblings or unrelated donors are available before PBSC allo-HSCT.

Eligibility criteria: Inclusion Criteria:

* PATIENT :

  * Age between 18 and 65 years ( included )
  * Being candidate to a graft of peripheral hematopoietic stem cells , according the following criteria :
* HLA compatibility 10 / 10 with the selected donor
* Malignant haematological disorder as described below :

  * Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia ( ALL) in 1st or 2d complete remission
  * Aggressive lymphoma in complete remission
  * Non - progressive myeloproliferative syndrome ,
  * Myelodysplasia with stable blasts is cell number and \< 10 % of blastocysts,
  * Acute leukemia biphenotypic in 1st or 2d complete remission
* Sequential graft conditioning, myeloablative or with a reduced intensity, both may include ATG
* Classical scheme for immunosuppression decrease ( from day 90 to day 180 ) • Not being opposed to medical data collection DONOR
* Adult ( ≥ 18 year old) up to the maximum authorized by each National Transplantation Authority
* Being a patient's sibling or registered in the Bone Marrow Donors Worldwide registry or a national registry
* Being candidate to a Peripheral Blood Stem Cells donation with a Human Leucocyt Antigen (HLA) 10 / 10 compatibility with the recipient ,
* Signed and dated informed consent ( in accordance with local regulation of the country in which the observation is performed )

Exclusion Criteria:

* Participating in a clinical trial, if interventional on the prophylaxis treatment ( not on the prophylaxis ) of GVHD, in the 30 days prior to the inclusion and during the Predictor 2 study ,
* Being placed under legal supervision ,
* Presenting any impossibility to fulfil the study requirements, due to geographical, social or physical reasons

Primary outcomes:
measure: Number of aGVHD of grade II to IV observed for the recipients
timeFrame: 3 month after allograft performance
Secondary outcomes:
measure: Evaluation of medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment
timeFrame: 3 month after allograft performance.
measure: Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment
timeFrame: 3 month after allograft performance.
measure: Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment
timeFrame: 3 month after allograft performance.
measure: Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment
timeFrame: 3 month after allograft performance.
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Z.N.A. Stuivenberg Ziekenhuis
city: Liège
country: Belgium
facility: CHU Liège
city: Wilrijk
country: Belgium
facility: U.Z. Antwerpen
city: Amiens
country: France
facility: CHU Amiens-Picardie
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: CHU de Caen
city: Clamart
country: France
facility: HIA Percy
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Limoges
country: France
facility: Hôpital Dupuyten
city: Nantes
country: France
facility: Hôtel Dieu
city: Nice
country: France
facility: CHU Nice
city: Paris
country: France
facility: Hôpital de la Pitiè-Salpétrière
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Pessac
country: France
facility: CHU Bordeaux
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU de Rennes
city: Saint-Priest-en-Jarez
country: France
facility: L'Institut de Cancérologie de la Loire
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU Nancy - Hôpital de Brabois
city: Dresden
country: Germany
facility: Donor Site-Dresden
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Köln
country: Germany
facility: Donor Site - Koln
Study officials:
affiliation: Head of adult hematology department
name: Olivier Hermine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rubio MT, Bouillie M, Bouazza N, Coman T, Trebeden-Negre H, Gomez A, Suarez F, Sibon D, Brignier A, Paubelle E, Nguyen-Khoc S, Cavazzana M, Lantz O, Mohty M, Urien S, Hermine O. Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease. Leukemia. 2017 Apr;31(4):903-912. doi: 10.1038/leu.2016.281. Epub 2016 Oct 14.