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

Part of paid clinical trials in St Louis, Missouri.

Sponsor
Washington University School of Medicine
Study ID
NCT06158828
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Rabbit Anti thymocyte globulin — DRUG
    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.
  • Busulfan — DRUG
    Busulfan is administered intravenously either Q6H or Q24H, with a recommended target Busulfan AUC of 70-90 mg\*h/L.
  • Fludarabine — DRUG
    Fludarabine is administered intravenously at a dose of 40 mg/m\^2/dose once daily for 4 days.
  • Thiotepa — DRUG
    Thiotepa is administered intravenously at a dose of 5 mg/kg/dose Q12H for 2 doses.
  • Melphalan — DRUG
    Melphalan is administered intravenously at a dose of 70 mg/m\^2/dose once daily for 2 days.
  • TCR alpha beta / CD19+ depleted haploidentical hematopoietic progenitor cell graft — BIOLOGICAL
    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.
  • memory-like natural killer cells — BIOLOGICAL
    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.
  • IL-2 — BIOLOGICAL
    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).
  • Plerixafor — DRUG
    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).
  • Granulocyte Colony-Stimulating Factor — BIOLOGICAL
    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.
  • CliniMACS — DEVICE
    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.

Study Details

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.

Key Dates

Start date
Nov 15, 2024
Status verified
Apr 2026
Primary completion
Sep 15, 2028
Completion
May 31, 2030

Study Design

Enrollment
68 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
    * Patients with high-risk genetic features \&/or poor response to upfront therapy * Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, \& Thiotepa on day -2 OR * Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2 * Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
  • Experimental: Cohort 2 Recipient: MAC or RIC + Cell graft + ML NK cell infusion
    * Patients with high-risk AML who meet certain criteria listed in the protocol * Myeloablative Conditioning (MAC): rabbit antithymocyte globulin (rATG), Busulfan, Fludarabine, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7, followed by Busulfan and Fludarabine from days -6 to -3, \& Thiotepa on day -2 OR * Reduced Intensity Conditioning (RIC): rabbit antithymocyte globulin (rATG), Fludarabine, Melphalan, and Thiotepa. All agents are administered intravenously. rATG is administered from days -9 to -7. Fludarabine is administered from day -8 to day -5, followed by Thiotepa on day -4 and Melphalan on days -3 and -2 * Patients will undergo infusion of the ex vivo TCRαβ/CD19+ depleted haploidentical HPC graft on day 0. On Day +7, patients will undergo infusion of the memory-like NK (ML NK) cells, followed by IL-2 subcutaneously 4 hours after the infusion. IL-2 will continue every other day through Day +19 for a maximum of 7 doses
  • Other: Donor
    Donors who meet the eligibility criteria will be mobilized as per institutional standard practice using G-CSF 10 mcg/kg/day for 5 consecutive days. Leukapheresis will be performed after 5 days of G-CSF administration (on Day -1) with a target volume for collection of 20 liters. If additional collection days are necessary to ensure target CD34+ doses, G-CSF administration may be extended per institutional standard and adjusted per physician discretion. Up to 4 days of pheresis are permitted.

Primary Outcome Measure

Safety of patients being administered donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant [ Time Frame: From transplant through Day +100 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Washington University School of MedicineSt LouisMissouri63110
Thomas M Pfeiffer, M.D.
[email protected]
314-273-2070
Thomas M Pfeiffer, M.D. (PRINCIPAL_INVESTIGATOR)
Amanda Cashen, M.D. (SUB_INVESTIGATOR)
Todd Fehniger, M.D., Ph.D. (SUB_INVESTIGATOR)
Shalini Shenoy, M.D. (SUB_INVESTIGATOR)
Robert Hayashi, M.D. (SUB_INVESTIGATOR)
Melissa Mavers, M.D., Ph.D. (SUB_INVESTIGATOR)
Rachel Langley, PharmD (SUB_INVESTIGATOR)
Feng Gao, Ph.D. (SUB_INVESTIGATOR)

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