Phase I Clinical Trial of ThINKK Adoptive Immunotherapy After Allogeneic Hematopoietic Transplantation in Children With Leukemia or Neuroblastoma (ThINKK-01)

April 2, 2026 updated by: Michel Duval

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1E8
        • The Hospital for Sick Children
        • Principal Investigator:
          • Joerg Krueger, MD
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H3T1C5

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Between 2 and less than 13 years old at time of informed consent form signature.
  2. Diagnosis of acute leukemia or neuroblastoma.
  3. Allogenic hematopoietic stem cell transplantation 30 to 90 days prior to eligibility confirmation.
  4. Blood NK cell counts ≥ 100 x 10E+6 cells/L at least once before eligibility confirmation.
  5. Life expectancy of ≥ 3 months per investigator's judgment at time of eligibility confirmation.
  6. 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.

Exclusion Criteria:

  1. Current grade 3 or 4 acute GvHD (per MAGIC criteria).

  2. Relapse of primary malignancy, or any other active malignancy.

    1. 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.
    2. For neuroblastoma, defined as a progressive disease.
  3. 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.
  4. Ongoing systemic therapy with cyclosporine.
  5. Administration or planned administration of any prohibited treatment listed in ad hoc section.
  6. Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times the upper limit of normal.
  7. Direct bilirubin serum levels ≥3 times the ULN (unless due to Gilbert syndrome).
  8. Baseline estimated glomerular filtration rate < 50 mL/min/1.73 m2, as determined using the Bedside Schwartz equation for < 18 years of age.
  9. Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated).
  10. O2 Sat saturation <90% on room air by pulse oximetry.
  11. Uncontrolled life-threatening symptomatic infection(s).
  12. Blood pressure below the 5th percentile for age, sex, and height last 24 hours.
  13. Ongoing therapy with intravenous vasopressor agent.
  14. 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.
  15. Pregnancy or breastfeeding or absence of highly effective methods of contraception for males and females of childbearing potential who engage in heterosexual intercourse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
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.
Other Names:
  • ThINKK

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of treatment-emergent adverse events and serious adverse events
Time Frame: From first study drug administration to 4 weeks after last administration
From first study drug administration to 4 weeks after last administration
Incidence of dose-limiting toxicities
Time Frame: From first study drug administration to 4 weeks after last administration
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
Time Frame: From first study drug administration to 4 weeks after last administration
From first study drug administration to 4 weeks after last administration

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients who received all infusions
Time Frame: At the end of week 4
At the end of week 4
Number of infusions received per patient
Time Frame: At the end of week 4
At the end of week 4
Time elapsed between confirmation of eligibility and first infusion
Time Frame: At day 1
At day 1
Percentage (%) of viable ThINKK cells at the time of infusion
Time Frame: Day of infusion
Day of infusion
Assessment of NK surface biomarkers
Time Frame: From first study drug administration to 1 week after last administration
From first study drug administration to 1 week after last administration
Assessment of plasmatic biomarkers by Olink®
Time Frame: From first study drug administration to 1 week after last administration
From first study drug administration to 1 week after last administration
Assessment of the global immune responses by single cell RNA sequencing
Time Frame: Prior to first infusion and up to 1 week post last infusion
Prior to first infusion and up to 1 week post last infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michel Duval

Collaborators

ExCellThera inc.
Héma-Québec
Centre C3i

Investigators

  • Principal Investigator: Michel Duval, MD, St. Justine's Hospital
  • Study Director: Sabine Herblot, PhD, St. Justine's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

February 20, 2026

First Submitted That Met QC Criteria

April 2, 2026

First Posted (Actual)

April 8, 2026

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 2, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ThINKK-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Currently reviewing our local regulations about individual patient data sharing (Canada)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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