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

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

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.

Sponsors & Collaborators

• The Leukemia and Lymphoma Society

  collaborator OTHER

• Rising Tide Foundation

  collaborator OTHER

• St. Louis Children's Hospital Foundation

  collaborator UNKNOWN

• Children's Discovery Institute

  collaborator OTHER

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Thomas M Pfeiffer, M.D. · Washington University School of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-11-15

Primary Completion

2028-09-15

Completion

2030-05-31

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations