Clinical trial NCT04494061: A Clinical Study to Investigate Interferon Gamma (IFNɣ) Signature in Patients Post HSCT and in Patients With Impaired HSC Proliferation Pre-transplant
Official title: A Clinical Study to Investigate Interferon Gamma (IFNɣ) Signature in Patients Post HSCT and in Patients With Impaired HSC Proliferation Pre-transplant
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Graft Failure
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: Cytel Inc.
name: BioMérieux
First posted: 2020-07-31
Enrollment: 101
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * Patients post HSCT at risk of graft failure based on their underlying diseases and on the transplant procedure.
* Patients with conditions where HSC proliferation is impaired (e.g. aplastic anemia) and with respective controls (healthy volunteers (HV)).

Brief summary: Clinical study designed to collect blood for research purposes in patients after hematopoietic stem cell transplantation (HSCT) or in patients with a medical condition where the blood cells production is impaired. The blood samples will be used to study the role of Interferon gamma (IFNɣ) in graft failure or impairment of hematopoietic stem cell proliferation. The IFNɣ signature will be assessed by measuring primarily IFNɣ and C-X-C Motif Chemokine Ligand 9 (CXCL9).

Detailed description: This clinical study is designed to investigate IFNγ activity in two cohorts of patients.

* First group will include patients post HSCT at risk of graft failure (GF) based on their underlying diseases and on the transplant procedure.
* Second group will contain patients with conditions where HSC proliferation is impaired (e.g. aplastic anemia) and with matched controls (healthy volunteers (HV) samples collected outside this clinical protocol).

IFNɣ activity will be assessed by measuring IFNγ and CXCL9 in serum.

For HSCT cohort, the following sampling time points are required: on day -7, pre HSCT on day 0, 1, 3, 5, 9, 13, 17, 21, 28, 31, 38 and one additional sample at the time when primary or secondary GF is suspected if not on the planned schedule. In addition, the following time points are recommended: day 7, 11, 15, 19, 24, 35, 42. It is also suggested to collect a sample when Graft vs Host Disease (GVHD) is diagnosed during any visit that the patients will attend as part of his/her standard treatment during the first 100 days post-transplant. The patient will be followed up until around day 100 post-transplant. This follow up will consist of capturing HSCT outcome information from patient hospital records around day 100.

For IHSCP cohort pre-transplant, it is recommended that, one sample per patient at the time of diagnosis (if possible not more than 1 week from the date of diagnosis) is collected. Age/sex matched control samples should be collected from healthy volunteers or patients with malignant disease outside of this protocol after appropriate consent.

Different sets of data will be collected for the HSCT and IHSCP cohorts respectively as described below:

Data collected for both cohorts

* Age and sex
* Inflammatory markers
* IFNɣ
* CXCL9
* Other potential relevant exploratory biomarkers
* Diagnosis
* Date of disease diagnosis
* Relevant medical history
* Date and time of sample collection

Data collected for HSCT cohort only

* Laboratory parameters assessed at the site laboratory on the date of sample collection and between collection dates when available:
* Absolute neutrophile count (ANC) and Platelets will be measured as per the schedule of assessment, if possible when routine monitoring of patient health is conducted
* Ferritin and Chimerism data will be collected when available (if measured as per site routine practice)
* Concomitant medications at the time of sample collection and between collection dates
* Presence of infection at the time of sample collection with the date of onset
* Presence of donor specific antibodies (DSA)
* Transplant information
* Date of start of conditioning
* Type of conditioning (Reduced Intensity Conditioning (RIC) / Myeloablative Conditioning (MAC) / Non-myeloablative Conditioning (NMAC) and medications
* Transplant details (donor type, degree of match, transplant manipulation, stem cell source)
* Date of transplant
* Date of primary / secondary GF or of confirmed engraftment
* GVHD with the date of onset
* Post-transplant treatment and date (Donor Lymphocyte Infusion (DLI), Stem Cell (SC) boost, growth factor, GVHD prophylaxis, second HSCT procedure)

Data collected for IHSCP cohort only

* Disease severity
* In addition, the following data will be recorded for pediatric patients up to 18 years old, if available:
* PNH clones
* History of hepatitis
* Karyotype

Study duration:

The study will be conducted, until the required number of patients is recruited.

* HSCT cohort: At patient level, the study will last about 100 days from pre-transplant blood collection to last follow up data collection around day 100 post HSCT, matching the standard HSCT patient care
* IHSCP cohort: At patient level the study will last 1 day.

Eligibility criteria: Inclusion Criteria:

* The patient must have consented to the use of their clinical data and biological samples for research investigations.
* In HSCT cohort:

  * Patients with underlying:

    i. non-malignant hematological disease (e.g. autoimmune and metabolic disorders, aplastic anemia, Sickle cell anemia, Fanconi anemia, Diamond-blackfan anemia, thalassemia, osteopetrosis, Wiskott-Aldrich syndrome, severe combined immunodeficiency) or ii. malignant disease with higher risk of GF, i.e. Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) with primary induction failure, second partial remission or relapse; Chronic Myeloid Leukemia (CML) in blastic phase (circulating blast or blast above 5% in biopsy); Non Hodgkin and Hodgkin Lymphoma and multiple myeloma with primary induction failure, second partial remission or relapse, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) with splenomegaly, myelofibrosis with portal hypertension pre-transplant, MDS/MPD overlap syndromes
  * and who received allogeneic HSCT and are at higher risk of graft failure based on at least one of the following criteria: i. Having received reduced intensity conditioning (RIC) or non myeloablative conditioning (NMA) combined with a non-malignant disease or having received graft from Bone Marrow (BM) ii. Ex vivo T cell depleted graft iii. Graft from mismatched unrelated donor or haploidentical donor iv. Graft from Umbilical Cord Blood (UCB)
* In the IHSCP cohort:

  * Patients with IHSCP pre-transplant (e.g. aplastic anemia)

Exclusion Criteria:

* HLH patients
* Body weight \< 10kg

Primary outcomes:
measure: HSCT cohort: IFNγ signature pre-and post-transplant
timeFrame: Day (-7) to day 100
measure: HSCT cohort: Relationship between IFNγ and the risk of graft failure
timeFrame: Day (-7) to day 100
measure: HSCT cohort: Relationship between IFNγ and the occurrence of GVHD
timeFrame: Day (-7) to day 100
measure: IHSCP cohort: IFNγ signature pre-transplant
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta - Campus Rumbeke
state: West-Vlaanderen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Caen cedex 9
country: France
facility: Hôpital Côte De Nacre
state: Basse-Normandie
city: Rennes cedex 9
country: France
facility: Hôpital Pontchaillou
state: Bretagne
city: Besançon Cedex
country: France
facility: Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz
state: Franche-Comte
city: Paris
country: France
facility: Hôpital Saint-Louis
state: Ile De France
city: Paris
country: France
facility: Hôpital Universitaire Robert-Debré
state: Ile-de-France
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpitaux de Brabois
state: Lorraine
city: Angers Cedex 9
country: France
facility: Centre Hosptitalier Universitaire d'Angers
state: Maine Et Loire
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
state: Nouvelle Aquitaine
city: Montpellier Cedex 5
country: France
facility: Hôpital Saint-Eloi
state: Provence Alpes Cote d'Azur
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
state: Provence Alpes Cote d'Azur
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
state: Rhone-Alpes
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire Estaing
state: Rhône
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
state: Lombardia
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
city: Genova
country: Italy
facility: Instituto Giannina Gaslini
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Torino
country: Italy
facility: Ospedale Regina Margherita
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum Kinderoncologie
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
state: Wales
city: London
country: United Kingdom
facility: The Royal Marsden Hospital - London
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust NHS Trust
Study officials:
affiliation: Hôpital Saint Louis Paris
name: Regis Peffault de Latour, MD
role: PRINCIPAL_INVESTIGATOR
References: