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

ConditionsLeukaemia (Acute Lymphoblastic)Leukaemia (Acute Myeloid)NeuroblastomaNeuroblastoma, MetastaticLeukaemia, Lymphoblastic, AcuteLeukemia Acute MyeloidLeukemia (Both ALL and AML)Leukemia Acute Myeloid - AMLHematopoetic Stem Cell TransplantationHematopoetic Stem Cell Transplant
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age2-12
SponsorMichel Duval

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

Treatment groups

12 Participants
are divided into 1 treatment group
Group A: TreatmentExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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
2

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)

Time frame
From first study drug administration to 4 weeks after last administration
3

Incidence and severity of treatment-related adverse events

Time frame
From first study drug administration to 4 weeks after last administration

Secondary outcomes

1

Number of patients who received all infusions

Time frame
At the end of week 4
2

Number of infusions received per patient

Time frame
At the end of week 4
3

Time elapsed between confirmation of eligibility and first infusion

Time frame
At day 1
4

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

Time frame
Day of infusion

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Michel Duval

Lead sponsor

St. Justine's Hospital

Sponsor institution

Héma-Québec

Collaborator

ExCellThera inc.

Collaborator

Centre C3i

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: