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

NCT07518654 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ThINKK-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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; Leukaemia (Acute Lymphoblastic)

Keywords

Thinkk; NK cells; pdc; immunotherapy

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of treatment-emergent adverse events and serious adverse events

  From first study drug administration to 4 weeks after last administration

• Incidence of dose-limiting toxicities

  Defined as: (1) Adverse event (excluding cytopenias) grade ≥ 3 considered to be possibly, probably or definitively related to the investigational product, (2) Cytopenia (anemia, neutropenia or thrombocytopenia) grade ≥ 4 considered to be possibly, probably or definitively related to the investigational product, (3) Grade ≥ 3 ICANS, (4) Grade ≥ 3 CRS and (5) Overall clinical grade ≥ 3 acute GvHD (MAGIC criteria)

  From first study drug administration to 4 weeks after last administration

• Incidence and severity of treatment-related adverse events

  From first study drug administration to 4 weeks after last administration

Secondary Outcomes (7)

• Number of patients who received all infusions

  At the end of week 4

• Number of infusions received per patient

  At the end of week 4

• Time elapsed between confirmation of eligibility and first infusion

  At day 1

• Percentage (%) of viable ThINKK cells at the time of infusion

  Day of infusion

• Assessment of NK surface biomarkers

  From first study drug administration to 1 week after last administration

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Therapeutic Inducers of Natural Killer Killing (ThINKK)

Interventions

Therapeutic Inducers of Natural Killer Killing (ThINKK) DRUG

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.

Also known as: ThINKK

Treatment

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Current grade 3 or 4 acute GvHD (per MAGIC criteria).
• Relapse of primary malignancy, or any other active malignancy.
• For neuroblastoma, defined as a progressive disease.
• 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.
• Administration or planned administration of any prohibited treatment listed in ad hoc section.
• 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.
• Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated).
• O2 Sat saturation \<90% on room air by pulse oximetry.
• Uncontrolled life-threatening symptomatic infection(s).
• Blood pressure below the 5th percentile for age, sex, and height last 24 hours.
• Ongoing therapy with intravenous vasopressor agent.
• 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.

Sponsors & Collaborators

• Michel Duval: lead
• Héma-Québec: collaborator
• ExCellThera inc.: collaborator
• Centre C3i: collaborator

Study Sites (2)

The Hospital for Sick Children

Toronto, Ontario, M5G1E8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T1C5, Canada

Location

Related Publications (7)

• Cordeau M, Belounis A, Lelaidier M, Cordeiro P, Sartelet H, Herblot S, Duval M. Efficient Killing of High Risk Neuroblastoma Using Natural Killer Cells Activated by Plasmacytoid Dendritic Cells. PLoS One. 2016 Oct 7;11(10):e0164401. doi: 10.1371/journal.pone.0164401. eCollection 2016.

  PMID: 27716850 BACKGROUND

• Belounis A, Ayoub M, Cordeiro P, Lemieux W, Teira P, Haddad E, Herblot S, Duval M. Patients' NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing. Cancer Immunol Immunother. 2020 Sep;69(9):1767-1779. doi: 10.1007/s00262-020-02581-0. Epub 2020 Apr 27.

  PMID: 32342128 BACKGROUND

• Poirier N, Paquin V, Leclerc S, Lisi V, Marmolejo C, Affia H, Cordeiro P, Theoret Y, Haddad E, Andelfinger G, Lavallee VP, Duval M, Herblot S. Therapeutic Inducers of Natural Killer cell Killing (ThINKK): preclinical assessment of safety and efficacy in allogeneic hematopoietic stem cell transplant settings. J Immunother Cancer. 2024 May 15;12(5):e008435. doi: 10.1136/jitc-2023-008435.

  PMID: 38754915 BACKGROUND

• Diaz-Rodriguez Y, Cordeiro P, Belounis A, Herblot S, Duval M. In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells. Cancer Immunol Immunother. 2017 Oct;66(10):1307-1320. doi: 10.1007/s00262-017-2022-y. Epub 2017 May 29.

  PMID: 28555259 BACKGROUND

• Lelaidier M, Diaz-Rodriguez Y, Cordeau M, Cordeiro P, Haddad E, Herblot S, Duval M. TRAIL-mediated killing of acute lymphoblastic leukemia by plasmacytoid dendritic cell-activated natural killer cells. Oncotarget. 2015 Oct 6;6(30):29440-55. doi: 10.18632/oncotarget.4984.

  PMID: 26320191 BACKGROUND

• Charrier E, Cordeiro P, Brito RM, Mezziani S, Herblot S, Le Deist F, Duval M. Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children. Bone Marrow Transplant. 2013 Mar;48(3):376-82. doi: 10.1038/bmt.2012.176. Epub 2012 Oct 15.

  PMID: 23064038 BACKGROUND

• Charrier E, Cordeiro P, Brito RM, Harnois M, Mezziani S, Herblot S, Le Deist F, Duval M. Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy. Biol Blood Marrow Transplant. 2014 Oct;20(10):1501-7. doi: 10.1016/j.bbmt.2014.06.007. Epub 2014 Aug 14.

  PMID: 25128615 BACKGROUND

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Neuroblastoma; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Paroxysmal nonkinesigenic dyskinesia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michel Duval, MD

  St. Justine's Hospital

  PRINCIPAL INVESTIGATOR

• Sabine Herblot, PhD

  St. Justine's Hospital

  STUDY DIRECTOR

Central Study Contacts

Michel Duval, MD

CONTACT

5143454931; michel.duval@umontreal.ca

Karine Leveille

CONTACT

5143454931; karine.leveille.hsj@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Pediatric Hemato-Oncologist, Cell Therapy Lab Director

Model Details: Adapted 3+3 design

Study Record Dates

• First Submitted: February 20, 2026
• First Posted: April 8, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

CA (2)