NCT07518654

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

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

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Michel Duval · Academic / Other
• Sex: All
• Age: 2 Years – 12 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Primary Objective: To assess the safety and tolerability of ThINKK adoptive immunotherapy by determination of the Maximum Tolerated Dose (MTD) in patients who has undergone allogenic HSCT for acute leukemia (ALL or AML) or neuroblastoma. * Secondary Objectives: * To demonstrate the feasibility of delivering (manufacturing and administrating) ThINKK adoptive immunotherapy after HSCT. * To assess biological effect at MTD (pharmacodynamic studies).

Conditions

• Leukaemia (Acute Lymphoblastic)
• Leukaemia (Acute Myeloid)
• Neuroblastoma
• Neuroblastoma, Metastatic
• Leukaemia, Lymphoblastic, Acute
• Leukemia Acute Myeloid
• Leukemia (Both ALL and AML)
• Leukemia Acute Myeloid - AML
• Hematopoetic Stem Cell Transplantation
• Hematopoetic Stem Cell Transplant

Interventions

Type	Name	Description
DRUG	Therapeutic Inducers of Natural Killer Killing (ThINKK)	This study uses an adaptation of the classical 3+3 dose-escalation model. The Maximum Tolerated Dose (MTD) is determined as the highest dose level at which six patients are treated with no unacceptable increase in acute GvHD risk and with no more than one patient experiencing a DLT. The first cohort (3 patients) will receive 7.5 M ThINKK/m2 weekly for 4 weeks. Dose distribution for the escalation levels will be guided by the pharmacodynamic data from the initial cohort.. If the preliminary data show that TRAIL expression remains stable at Day +8, dose level 2 will be set at 15 × 10\^6 / m2 BSA weekly, and dose level 3 at 30 × 10\^6 / m2 BSA weekly. If the data instead indicate the need to shorten the dosing interval to maintain TRAIL expression, dose level 2 will be set at 7.5 × 10\^6 / m2 BSA bi-weekly and dose level 3 at 15 × 10\^6 / m2 BSA bi-weekly.

Timeline

• Start date: 2026-05-01
• Primary completion: 2029-05-01
• Completion: 2029-05-01
• First posted: 2026-04-08
• Last updated: 2026-04-08

Locations

2 sites across 1 country: Canada