Phase I Clinical Trial of ThINKK Adoptive Immunotherapy After Allogeneic Hematopoietic Transplantation in Children With Leukemia or Neuroblastoma

A vizsgálat adatai

Ki végzi

Michel Duval

Azonosító

NCT07518654

A regiszteradat frissítve

2026. április 8.

Eredeti leírás

A first-in-class adoptive immunotherapy we called ThINKK, for Therapeutic Inducers of Natural Killer (NK) cell Killing, have been designed for use after hematopoietic stem cell transplantation (HSCT), where the proper stimulation of graft-derived NK cells has been shown to prevent relapse.A teljes eredeti leírásKevesebb

Phase I Clinical Trial of Therapeutic Inducers of Natural Killer Killing (ThINKK) Adoptive Immunotherapy: Feasibility, Safety and Pharmacodynamics in Children Undergoing Allogenic Hematopoietic Transplantation for Leukemia or Neuroblastoma

A first-in-class adoptive immunotherapy we called ThINKK, for Therapeutic Inducers of Natural Killer (NK) cell Killing, have been designed for use after hematopoietic stem cell transplantation (HSCT), where the proper stimulation of graft-derived NK cells has been shown to prevent relapse.

ThINKK immunotherapy builds on our earlier research on NK cells and plasmacytoid dendritic cells (PDC) in cord blood and after HSCT. PDC are the sentinels of the immune system. Upon viral nucleic acids detection, PDC secrete a vast array of chemokines and cytokines that stimulate NK cells. PDC stimulation enhances NK cells killing of infected cells that express stress-induced molecules. Cancer cells also express stress-related molecules at their surface. However, NK cells do not receive PDC stimulation when fighting cancer. ThINKK therapy is designed to provide this necessary stimulation.

Bevonási feltételek: Between 2 and less than 13 years old at time of informed consent form signature; Diagnosis of acute leukemia or neuroblastoma; Allogenic hematopoietic stem cell transplantation 30 to 90 days prior to eligibility confirmation; Blood NK cell counts ≥ 100 x 10E+6 cells/L at least once before eligibility confirmation; Life expectancy of ≥ 3 months per investigator's judgment at time of eligibility confirmation; Patient or legally acceptable representative has provided informed consent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.

Kizáró feltételek: Ongoing therapy with systemic corticosteroids (equivalent to a prednisone dose >0.5 mg/kg/day). Patients actively undergoing corticosteroid tapering during Screening may be enrolled once they have reached a prednisone-equivalent dose ≤ 0.5 mg/kg/day with Sponsor-Investigator approval, with the expectation that the taper will continue; Ongoing systemic therapy with cyclosporine; Ongoing therapy with intravenous vasopressor agent; Relapse of primary malignancy, or any other active malignancy; For leukemia, defined as either morphological relapse or Minimal Residual Disease (MRD) ≥0.01% as measured by flow cytometry. MRD detected by polymerase chain reaction (PCR) does not constitute an exclusion criterion; For neuroblastoma, defined as a progressive disease; Uncontrolled life-threatening symptomatic infection(s); Any condition that, in the opinion of the Investigator, would compromise the safety of the patient, would prevent full participation in this study, or would interfere with the evaluation of any study endpoints; Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times the upper limit of normal; Direct bilirubin serum levels ≥3 times the ULN (unless due to Gilbert syndrome); Baseline estimated glomerular filtration rate < 50 mL/min/1.73 m2, as determined using the Bedside Schwartz equation for < 18 years of age; Blood pressure below the 5th percentile for age, sex, and height last 24 hours; Current grade 3 or 4 acute GvHD (per MAGIC criteria); Administration or planned administration of any prohibited treatment listed in ad hoc section; Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated); O2 Sat saturation <90% on room air by pulse oximetry; Pregnancy or breastfeeding or absence of highly effective methods of contraception for males and females of childbearing potential who engage in heterosexual intercourse.

ClinicalTrials.gov NCT07518654