- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04882605
KIR Sequencing and Typing for Allograft in Nancy (KIR-STAN)
Application of the Major Predictive Scoring Strategies Assessing KIR-based NK Alloreactivity to Donor/Recipient Couples
The use of haploidentical donors for aHSCT has greatly increased this past decade leading to a major paradigm shift: while finding 10/10 HLA-matched donors represented the prior difficulty for decades, the current problem is about finding the best haploidentical donor among several potential ones. The prediction of NK cells alloreactivity toward leukemic cells provides promising perspectives, although the underlying biological processes remain unclear. To date, many prediction models based on KIR and MHC genotyping have been designed and used across studies, which contribute to blur clinical conclusions.
The investigators hypothesized that the diversity of models used to predict NK alloreactivity in aHSCT could partly be responsible for the current literature discrepancies. The main objective of this work consisted of applying the major KIR-based prediction models in D/R couples undergoing aHSCT in different fashions - with MSD and haploidentical donors - to describe their heterogeneity and potential correlations. As clinical data were available for these two cohorts, the investigators described correlations that could be assessed between the scoring strategies and the clinical outcomes.
As suspected, it was highlighted that the different scoring strategies greatly impact the assessment of alloreactivity within D/R couples. As an example, two broadly used scoring strategies - educational models and missing-ligand models - show clear opposite predictions. Moreover, some scoring strategies seem to be better adapted to genoidentical or haploidentical cohorts, whereas others are robust across the different cohorts. Concerning the clinical-biological correlations, it was highlighted that (i) each scoring strategy is differentially associated to the different outcomes (ii) the different scoring strategies predict one particular outcome with different efficacy (iii) the D/R compatibility greatly impacts the pertinence of the scoring strategy.
This work therefore contributes to unravel the KIR-based alloreactivity prediction of NK cells in aHSCT. This would help to overcome the current literature discrepancies in this field as in making new hypotheses to better understand and predict NK alloreactivity to further develop its use in medical practice.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
COHORT 1 = Matched Sibling Donors couples (MSD couples) INCLUSION CRITERIA
- recipient of HSCT selected from the French national database CRYOSTEM
- adult patients (18-50 years old)
- transplanted in first remission
- receiving myeloablative conditioning without anti-thymoglobulin
- 16 couples without any sign of GVH (8 males and 8 females)
- 16 couples with aGVH without cGVH
- 9 couples with cGVH without aGVH
- 9 couples with both cGVH and aGVH. EXCLUSION CRITERIA
- insufficient DNA material after Miltenyi extraction
COHORT 2 = Haploidentical couples INCLUSION CRITERIA
- patient undergoing a haploidentical HSCT in the Hematology Department of Nancy's University Hospital, Lorraine, France (French Minister registration number : DC-2020-4068) EXCLUSION CRITERIA
- insufficient DNA material after Miltenyi extraction (7 MSD couples)
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Donor/recipient couple with Matched Sibling Donor
Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation + its 10/10 HLA-matched donor recruited among his siblings |
Allelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology.
Allelic genotyping resolution of all 13 KIR genes (KIR2DL1, KIR2DL2/2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS3/2DS5, KIR2DS4, KIR3DL1/3DS1, KIR3DL2, KIR3DL3), 2 KIR pseudogenes (KIR2DP1 and -3DP1) using Illumina technology.
Compiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores
|
Donor/recipient couple with Haploidentical Donor
Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation + its 5/10 HLA-matched donor recruited among his relatives |
Allelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology.
Allelic genotyping resolution of all 13 KIR genes (KIR2DL1, KIR2DL2/2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS3/2DS5, KIR2DS4, KIR3DL1/3DS1, KIR3DL2, KIR3DL3), 2 KIR pseudogenes (KIR2DP1 and -3DP1) using Illumina technology.
Compiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity
Time Frame: At inclusion
|
At inclusion
|
Describe the potential correlations between a KIR-based prediction models and post-allograft outcomes
Time Frame: at least 4 months
|
at least 4 months
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2020PI142
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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