NCT06158828

Pilot Study of Memory-like Natural Killer (ML NK) Cells After TCRαβ T Cell Depleted Haploidentical Transplant in AML

A Phase I/II Pilot Study of Memory-like NK Cells to Consolidate TCRαβ T Cell Depleted Haploidentical Transplant in High-risk AML

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial represents a single institution phase I/II pilot study with the primary objective of establishing the safety and feasibility of generating and infusing ML NK cells after TCRαβ haplo-HCT.

Conditions

• AML, Childhood
• Aml
• Acute Myeloid Leukemia, Pediatric
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Rabbit Anti thymocyte globulin	rATG is administered intravenously over 6-18 hours for a total of 2 to 3 doses. The daily dose is based on body weight and lymphocyte count.
DRUG	Busulfan	Busulfan is administered intravenously either Q6H or Q24H, with a recommended target Busulfan AUC of 70-90 mg\*h/L.
DRUG	Fludarabine	Fludarabine is administered intravenously at a dose of 40 mg/m\^2/dose once daily for 4 days.
DRUG	Thiotepa	Thiotepa is administered intravenously at a dose of 5 mg/kg/dose Q12H for 2 doses.
DRUG	Melphalan	Melphalan is administered intravenously at a dose of 70 mg/m\^2/dose once daily for 2 days.
BIOLOGICAL	TCR alpha beta / CD19+ depleted haploidentical hematopoietic progenitor cell graft	The HPC product obtained from a haploidentical donor will undergo ex vivo TCR alpha beta and CD19+ depletion, and will be infused fresh on Day 0. There is no maximum limit for CD34+ dose. A maximum dose of 1 x 10\^5/kg recipient weight of TCRαβ cells should not be exceeded in the final HPC product.
BIOLOGICAL	memory-like natural killer cells	The ML NK cells (dose: max capped at 20 x 10\^6/kg recipient weight, minimum dose allowed is 0.5 x 10\^6/kg recipient weight) will be infused on Day +7.
BIOLOGICAL	IL-2	IL-2 is administered subcutaneously at a dose of 1 million units/m\^2 on Days +7, +9, +11, +13, +15, +17, and +19 (7 doses total).
DRUG	Plerixafor	If suboptimal collection of stem cells is predicted, plerixafor may be administered at a dose of 0.24 mg/kg subcutaneous injection once (maximum 40mg/dose). For patients with renal impairment, plerixafor will be administered at a dose of 0.16 mg/kg subcutaneous injection (maximum 27 mg/day).
BIOLOGICAL	Granulocyte Colony-Stimulating Factor	G-CSF will be administered at a dose of 10 mcg/kg/day for 5 days, or 6 days if two days of collection are needed.
DEVICE	CliniMACS	After stem cells are collected by leukapheresis, in order to create the HPC product, the stem cells will be washed to remove platelets and the cell concentration will be adjusted per laboratory and CliniMACS technology recommendations. The cells are then labeled using the CliniMACS TCRαβ Biotin Kit and CD19+ immunomagnetic microbeads. After labeling, the cells are washed to remove unbound microbeads. The partially processed product is loaded on the CliniMACS device where labeled cells are depleted and the negative fraction is eluted off the device. The negative fraction is centrifuged and volume reconstituted to obtain the final product.

Timeline

• Start date: 2024-05-15
• Primary completion: 2028-09-15
• Completion: 2030-05-31
• First posted: 2023-12-06
• Last updated: 2026-02-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study