Leukaemia (Acute Lymphoblastic)Phase 1ThINKK-01NCT07518654
Phase I Clinical Trial of ThINKK Adoptive Immunotherapy After Allogeneic Hematopoietic Transplantation in Children With Leukemia or Neuroblastoma
A Phase 1 study testing Therapeutic Inducers of Natural Killer Killing (ThINKK) in people with Leukaemia (Acute Lymphoblastic) and Leukaemia (Acute Myeloid), run by Michel Duval at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Leukaemia (Acute Lymphoblastic), Leukaemia (Acute Myeloid), Neuroblastoma
- What is being tested?
- Therapeutic Inducers of Natural Killer Killing (ThINKK)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesCanada
- Study dates
- 1 May 2026to 1 May 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- Current grade 3 or 4 acute GvHD (per MAGIC criteria).
- 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.
- 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.
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- 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.
- Pregnancy or breastfeeding or absence of highly effective methods of contraception for males and females of childbearing potential who engage in heterosexual intercourse
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites
CHU Sainte-Justine
Montreal, Quebec, H3T1C5
Henrique Bittencourt, MD, 5143454931 ext. 2724, henrique.bittencourt.med@ssss.gouv.qc.ca
Henrique Bittencourt, MD
The Hospital for Sick Children
Toronto, Ontario, M5G1E8
Joerg Krueger, MD, 4168131500, joerg.krueger@sickkids.ca
Joerg Krueger, MD
About this study
Official title: 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.
Read the 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
- Being tested
- Therapeutic Inducers of Natural Killer Killing (ThINKK)
- Keywords
- Thinkk, NK cells, pdc, immunotherapy
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Neuroblastoma, Neoplasm Metastasis, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Paroxysmal nonkinesigenic dyskinesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic Inducers of Natural Killer Killing (ThINKK)Drug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: Therapeutic Inducers of Natural Killer Killing (ThINKK) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-emergent adverse events and serious adverse events
Measured: 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)
Measured: From first study drug administration to 4 weeks after last administration
Incidence and severity of treatment-related adverse events
Measured: From first study drug administration to 4 weeks after last administration
Secondary outcomes (7)
Number of patients who received all infusions
Measured: At the end of week 4
Number of infusions received per patient
Measured: At the end of week 4
Time elapsed between confirmation of eligibility and first infusion
Measured: At day 1
Percentage (%) of viable ThINKK cells at the time of infusion
Measured: Day of infusion
Assessment of NK surface biomarkers
Measured: From first study drug administration to 1 week after last administration
Assessment of plasmatic biomarkers by Olink®
Measured: From first study drug administration to 1 week after last administration
Assessment of the global immune responses by single cell RNA sequencing
Measured: Prior to first infusion and up to 1 week post last infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start1 May 2026 (estimated)
- Primary completion1 May 2029 (estimated)
- Study completion1 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Leukaemia (Acute Lymphoblastic)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Adapted 3+3 design
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michel Duval
- Sponsor type
- University, hospital or other
- Collaborators
- Héma-Québec, ExCellThera inc., Centre C3i
- Responsible party
- Sponsor-investigator, Michel Duval, St. Justine's Hospital
- Investigators
- Michel Duval, MD, Principal investigator, St. Justine's HospitalSabine Herblot, PhD, Study director, St. Justine's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07518654
- Sponsor's protocol ID
- ThINKK-01
- Acronym
- ThINKK-01
- Status last verified
- Apr 2026
- First submitted
- 20 Feb 2026
- Last updated
- 8 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Currently reviewing our local regulations about individual patient data sharing (Canada)
Publications
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.
PubMed 27716850Belounis 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.
PubMed 32342128Poirier 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.
PubMed 38754915Diaz-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.
PubMed 28555259Lelaidier 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.
PubMed 26320191Charrier 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.
PubMed 23064038Charrier 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.
PubMed 25128615