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

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).

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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