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Abatacept Mediated Natural Killer Cell-Based Immunotherapy

Phase 2
Conditions
Health Condition 1: D759- Disease of blood and blood-formingorgans, unspecified
Registration Number
CTRI/2021/09/036713
Lead Sponsor
Manashi Chakrabarti Foundation
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Yet Recruiting
Sex
Not specified
Target Recruitment
0
Inclusion Criteria

· First allogeneic transplant.

· Age between 2 and 65 years.

· Patients must have a related donor that is HLA-matched at least 5 of 10 HLA A, B, C, DRB1, DQB.

· Cardiac function: Shortening fraction >25%; ejection fraction >40%

· Estimated creatinine clearance greater than 50 mL/minute

· Pulmonary function: DLCO >=40% (adjusted for hemoglobin) and FEV1>=70%, oxygen saturation >91%

· Liver function: direct (conjugated) bilirubin < 2x the upper limit of normal and ALT/AST < 2.5x the upper normal limit

· No major organ disfunction

· Signed informed consent

Exclusion Criteria

· Life expectancy less than 6 months

· Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.

· Pregnant or breastfeeding patients

· Patients seropositive for the human immunodeficiency virus (HIV)

· Patient with active Hepatitis B or C determined by serology and/or NAAT not on treatment

· Active hepatitis, bridging fibrosis or cirrhosis on liver biopsy (biopsy required for patients on chronic transfusion therapy for > 1 year and evidence of iron overload with ferritin >1000 ng/mL)

· Patients with suitable 10/10 HLA matched related and unrelated donors

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
The potential of CTLA4Ig in sparing and/or potentiating NK cell cytotoxicity is an unexplored and yet an exciting possibility in the field of cellular therapy with initial clinical data strongly suggesting a favourable impact of the molecule on NK cell function. This study will help in establishment of the mechanistic pathway underlying this phenomenon. <br/ ><br>The exploration of the crosstalk between NK cells and monocyte/macrophages might uncover hitherto unknown pathways by which anti-leukemia activity of NK cells is potentiated. <br/ ><br>Timepoint: 24 months
Secondary Outcome Measures
NameTimeMethod
The translational impact of unraveling the interaction between NK cells and monocyte/macrophages on exposure to CTLA4Ig might have a far-reaching impact in the field of cellular therapy, wherein a unique and more importantly, an affordable scalable platform for NK cell-based immunotherapy could be established, both in the context of HCT and without HCT.Timepoint: 24 months
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