Evaluation of a Donor Testing Kit for the Prediction of AGVHD in Patient Receiving a Peripheral Blood Stem Cell Allograft

Acute Lymphoblastic Leukemia Clinical Trial

— Predictor2  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03887156
• Other study ID #: K180304J
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 16, 2019
• Est. completion date: March 16, 2023

Study information

• Verified date: September 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Yannick VACHER
• Phone: +33 1 44 84 17 30
• Email: yannick.vacher[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 227
• Est. completion date: March 16, 2023
• Est. primary completion date: March 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia Biphenotypic in Remission
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia in Remission
• Leukemia
• Lymphoma in Remission
• Myelodysplasia With Stable Blasts is Cell Number and < 10% of Blastocysts
• Myelodysplastic Syndromes
• Non-progressive Myeloproliferative Syndrome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Diagnostic Test:
• Ex vivo capacities of CD4neg INkT expansion of the peripheral blood donor with the Predictor test
Calculation of ex vivo capacities of CD4neg INkT expansion of the peripheral blood from an identified donor for an allograft. Sample is collected before mobilization and the blood culture and analysis using the Predictor test are performed by the central lab.

Locations

Country	Name	City	State
Belgium	Z.N.A. Stuivenberg Ziekenhuis	Antwerpen
Belgium	CHU Liège	Liège
Belgium	U.Z. Antwerpen	Wilrijk
France	CHU Amiens-Picardie	Amiens
France	CHU Angers	Angers
France	CHU de Caen	Caen
France	HIA Percy	Clamart
France	CHU Clermont-Ferrand	Clermont-Ferrand
France	Hôpital Dupuyten	Limoges
France	Hôtel Dieu	Nantes
France	CHU Nice	Nice
France	Hôpital de la Pitiè-Salpétrière	Paris
France	Hôpital Necker Enfants Malades	Paris
France	CHU Bordeaux	Pessac
France	CHU de Poitiers	Poitiers
France	CHU de Rennes	Rennes
France	L'Institut de Cancérologie de la Loire	Saint-Priest-en-Jarez
France	Institut Universitaire du Cancer de Toulouse	Toulouse
France	CHRU Nancy - Hôpital de Brabois	Vandœuvre-lès-Nancy
Germany	Donor Site-Dresden	Dresden
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Donor Site - Koln	Köln

Sponsors (6)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Axonal-Biostatem, CERBA laboratory, Imagine Institute, SATT, SNC Graft Versus Host Disease

Countries where clinical trial is conducted

Belgium,  France,  Germany, 

References & Publications (1)

Rubio MT, Bouillié M, Bouazza N, Coman T, Trebeden-Nègre 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of aGVHD of grade II to IV observed for the recipients	To predict the risk of acute GVHD. Number of aGVHD of grade II to IV observed for the recipients in the 3 months after the graft and results of the Predictor test, before graft, on their own donor's blood.	3 month after allograft performance
Secondary	Evaluation of medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment	Number of hospitalization or medical consultation, exams, concomitant treatments.	3 month after allograft performance.
Secondary	Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment	Number of medical consultations	3 month after allograft performance.
Secondary	Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment	Number of exams	3 month after allograft performance.
Secondary	Evaluation of the medico-economic aspect of the Predictor test Total estimated cost of the aGVHD treatment	Number of concomitant treatments	3 month after allograft performance.