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RecruitingNCT06158828ABCD-NKUpdated Aug 24, 2026

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

A Phase 1/2 interventional study of Rabbit Anti thymocyte globulin and Busulfan in AML, Childhood, Aml and Acute Myeloid Leukemia, Pediatric, sponsored by Washington University School of Medicine. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-24.

Sponsored by Washington University School of Medicine · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Nov 2024; still recruiting 1 year 10 months later.
Phase
Phase 1/2
Study type
Interventional
Enrollment
68
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

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

Keywords

  • high-risk AML
  • haploidentical transplant
  • high-risk acute myeloid leukemia
  • AML from MDS
  • memory-like natural killer cells
  • ML NK cells
03

In context

Leukemia, Myeloid, Acute

2,971 studies on the registry are indexed under Leukemia, Myeloid, Acute; 745 are open to participants now.

This study's planned enrollment of 68 is above the median of 41 across 2,509 interventional studies indexed under Leukemia, Myeloid, Acute.

Browse Leukemia, Myeloid, Acute studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Patient Inclusion Criteria - Cohort 1:

  1. High risk acute myeloid leukemia (AML) in either:

    1. Complete remission (CR) defined by \< 5% marrow blasts by morphology in the context of hematological recovery (ANC ≥ 0.5× 10\^9/L, platelet count ≥ 50 × 10\^9/L).
    2. Morphological leukemia free state (MLFS) defined by the absence of hematological recovery and \< 5% marrow blasts by morphology

  2. Patients must further meet one of the below for inclusion into the study:

    1. De novo AML in CR1 with any of the following high-risk features:

      • MRD ≥ 1% after first induction course
      • MRD ≥ 0.1% after second induction course
      • RPN1-MECOM
      • RUNX1-MECOM
      • NPM1-MLF1
      • DEK-NUP214
      • KAT6A-CREBBP (if ≥ 90 days at diagnosis)
      • FUS-ERG
      • KMT2A-AFF1
      • KMT2A-AFDN
      • KMT2A-ABI1
      • KMT2A-MLLT1
      • 11p15 rearrangement (NUP98 - any partner gene)
      • 12p13.2 rearrangement (ETV6 - any partner gene)
      • Deletion 12p to include 12p13.2 (loss of ETV6)
      • Monosomy 5/Del(5q) to include 5q31 (loss of EGR1)
      • Monosomy 7
      • 10p12.3 rearrangement (MLLT10 - any partner gene)
      • FLT3/ITD with allelic ratio > 0.1%, without bZIP CEBPA or NPM1
      • RAM phenotype as evidenced by flow cytometry
      • Other high-risk features not explicitly stated here, after discussion/approval with protocol PI.
    2. De novo AML in ≥ CR2
    3. Therapy-related AML in CR1
    4. AML evolving from myelodysplastic syndrome (MDS)
  3. One prior hematopoietic cell transplant is allowed, provided remission criteria as defined above are met.

Patient Inclusion Criteria - Cohort 2:

  1. High risk acute myeloid leukemia (AML) defined by either of the following:

    1. Treatment refractory disease: AML that is not in complete remission despite prior standard or salvage therapies.
    2. Multiply relapsed disease: AML that has relapsed after 2 or more hematopoietic cell transplantations.

  2. BM disease burden criteria:

    1. Bone marrow blasts must be \<25% by morphologic assessment on aspirate smear, based on a manual differential count of at least 200 nucleated cells.
    2. If an absolute discrepancy of ≥ 20 percentage points exists between morphologic blast evaluation and ancillary studies - including flow cytometry, cytogenetics, and molecular analyses, eligibility determination is at the investigator's discretion.
    3. Hypocellular / Aplastic Marrow Exception: If bone marrow cellularity on core biopsy is less than 25%, the blast percentage threshold and the 200-cell minimum differential count requirement are waived.

Patient Inclusion Criteria - Both Cohorts:

  1. Less than or equal to 40 years of age.
  2. Lansky (\<16 years) or Karnofsky (≥16 years) performance status of >60%.

  3. Adequate organ function as defined below:

    1. Total bilirubin ≤ 3 x IULN for age
    2. AST(SGOT)/ALT(SGPT) ≤ 5 x IULN for age
    3. GFR ≥ 60 mL/min/1.73m2 as estimated by (1) updated Schwartz formula for ages 1-17 years or Cockcroft-Gault formula for ages ≥ 18 years, (2) 24-hour creatinine clearance, or (3) renal scintigraphy. If GFR is abnormal for age based on updated Schwartz or Cockcroft-Gault formula, accurate measurement should be obtained by either 24-hour creatinine clearance or renal scintigraphy.
    4. Renal function may also be estimated by serum creatinine based on age/gender. A serum creatinine \< 2 x IULN for age/gender is required for inclusion on this protocol.
  4. Adequate cardiac function, defined by left ventricular ejection fraction (LVEF) at rest ≥50% or shortening fraction (SF) ≥27% (via echocardiogram or MUGA).

  5. Adequate pulmonary function, defined by:

    1. FEV1, FVC, and DLCO ≥50% of predicted.
    2. O2 saturation ≥ 92% on room air by pulse oximetry and no supplemental O2 at rest for children \< 8 years of age or those unable to perform pulmonary function testing (PFT). For children unable to perform PFT, a high-resolution CT chest should be obtained.
  6. The effects of these treatments on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 24 months following transplant. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  7. Ability to understand and willingness to sign an IRB approved written informed consent document, or patient has a guardian who has the ability to understand and willingness to sign an IRB approved written informed consent document.
  8. Available familial haploidentical donor. The HCT donor must be available and willing to undergo 2 leukapheresis procedures: (I) one mobilized collection for the HPC graft and (II) one non-mobilized leukapheresis collection for the manufacturing of ML NK cells.
  9. Donor and recipient must be identical at a minimum of one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA- DQB1. A minimum of 5/10 match is required and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.

Patient Exclusion Criteria - Both Cohorts

  1. Active GvHD. If patient had prior GvHD, patient must be off immunosuppression for at least 3 months prior to starting study treatment.
  2. Active non-hematologic malignancy. History of other malignancy is acceptable as long as therapy has been completed and there is no current evidence of disease.
  3. Currently receiving any other investigational agents at the time of transplant.
  4. Active CNS or extramedullary disease. History of CNS or extramedullary disease currently in remission is acceptable.
  5. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study.
  6. Inability to discontinue medications that are likely to interfere with ML NK cell activity, i.e., glucocorticoids and other immunosuppressants.
  7. Presence of significant anti-donor HLA antibodies per institutional standards. Anti-donor HLA - Antibody Testing is defined as a positive crossmatch test of any titer (by complement dependent cytotoxicity or flow cytometric testing) or the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay > 3000.
  8. Presence of a second major disorder deemed a contraindication for HCT.
  9. Patients with Fanconi Anemia or Down Syndrome.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, viral with clinical instability, or fungal), symptomatic congestive heart failure, or unstable cardiac arrhythmia.
  11. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of the start of conditioning.

Donor Eligibility Criteria - Both Cohorts

  1. The preferred donor should be an adult aged 18 years or older. However, in circumstances where no suitable adult donor is available, consideration may be given to a minor donor aged 12 years or older. This exception only applies when all identified, otherwise eligible adult donors meet one or more of the following criteria:

    • A medical condition that poses unacceptable risk, including autoimmune disease, infection, hematologic disorder, malignancy or a pathogenic germline mutation.
    • Comorbidities that preclude safe administration of granulocyte colony-stimulating factor (G-CSF), placement of a pheresis catheter and/or stem cell collection.
    • Served as donor in prior haploidentical HCT.
    • Significant psychosocial or logistical barriers.
  2. Donor must be HLA haploidentical (≥ 5/10 and ≤ 9/10 allele match at the -A, -B, -C, DRB1 and DQ loci) by high resolution typing and related to the patient.
  3. Donor must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
  4. Donor must be available and willing to undergo one mobilized and one non-mobilized leukapheresis procedure.
  5. Donor may not be pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiation of recipient's conditioning regimen, within 7 days of donor stem cell mobilization regimen and prior to second non-mobilized leukapheresis..
  6. Donor must be able to understand and willing to sign an IRB-approved written informed consent document.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
68 participants (estimated)

Study 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.

    Drug: Plerixafor · Biological: Granulocyte Colony-Stimulating Factor

Interventions

  • DrugRabbit 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.

    Also known as: rATG

  • DrugBusulfan

    Busulfan is administered intravenously either Q6H or Q24H, with a recommended target Busulfan AUC of 70-90 mg\*h/L.

  • DrugFludarabine

    Fludarabine is administered intravenously at a dose of 40 mg/m\^2/dose once daily for 4 days.

  • DrugThiotepa

    Thiotepa is administered intravenously at a dose of 5 mg/kg/dose Q12H for 2 doses.

  • DrugMelphalan

    Melphalan is administered intravenously at a dose of 70 mg/m\^2/dose once daily for 2 days.

    Also known as: Evolema, Alkeran

  • BiologicalTCR 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.

    Also known as: TCRab/CD19+ depleted haploidentical HPC graft

  • Biologicalmemory-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.

    Also known as: ML NK cells

  • BiologicalIL-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).

  • DrugPlerixafor

    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).

  • BiologicalGranulocyte 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.

    Also known as: G-CSF

  • DeviceCliniMACS

    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.

06

What researchers measure

Primary outcomes

  1. Safety of patients being administered donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant

    Safety will be determined by events occurring following transplant. Non-relapse mortality, engraftment failure, and development of severe GvHD will be considered events.

    Time frame: From transplant through Day +100

  2. Feasibility of manufacturing and administering donor-derived ML NK cells following TCR alpha beta depleted haploidentical cell transplant

    Feasibility is defined by product manufacture failure, i.e., the inability to infuse ML NK cells due to product contamination or insufficient cell dose (\<0.5x10\^6 / kg recipient weight).

    Time frame: Through time of ML NK cell infusion (around Day +7)

Secondary outcomes

  1. Relapse Free Survival (RFS)

    Defined as the time between the date of transplant and date of last follow up, relapse, or death due to any cause.

    Time frame: From transplant through Month 12

  2. Overall Survival (OS)

    Defined as death from any cause following transplant.

    Time frame: From transplant through Month 12

  3. Development of acute graft versus host disease (aGvHD)

    Incidence of grade II, III, or IV acute GvHD as graded according to the NIH consensus criteria. Severe aGvHD (Grades III-IV) is considered an event.

    Time frame: From transplant through Day +100

  4. Development of chronic graft versus host disease (cGvHD)

    Incidence of chronic GvHD as graded according to the NIH consensus criteria. Severe cGvHD is considered an event.

    Time frame: From transplant through Day +180

  5. Development of chronic graft versus host disease (cGvHD)

    Incidence and severity of chronic GvHD as graded according to the NIH consensus criteria. Severe cGvHD is considered an event.

    Time frame: From transplant through Day +365

  6. Development of infections

    Significant infections include, but are not limited to, bacterial or fungal sepsis, viral reactivation with or without clinical disease, other viral infections, and community acquired infections.

    Time frame: From transplant through Day +180

  7. Analysis of immune reconstitution

    Immune reconstitution is defined as regain of function of donor-derived immunogenic cells and is measured by recovery of individual cellular compartments.

    Time frame: From transplant through Month 24

07

Study locations

1 of 1 sites recruiting
  • Washington University School of Medicine
    St Louis, Missouri 63110, United States
    • Thomas M Pfeiffer, M.D. · Contact · pthomas@wustl.edu · 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
    Recruiting
08

References and documents

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 24, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06158828
Lead sponsor
Washington University School of Medicine
Collaborators
The Leukemia and Lymphoma Society, Rising Tide Foundation, St. Louis Children's Hospital Foundation, Children's Discovery Institute, Hyundai Hope On Wheels
Responsible party
Sponsor
First posted
Dec 6, 2023
Start date
Nov 15, 2024
Primary completion
Sep 15, 2028 (estimated)
Completion
May 31, 2030 (estimated)
Last update
Aug 24, 2026

Study contacts

Thomas M Pfeiffer, M.D.
Contact
pthomas@wustl.edu
314-273-2070
Thomas M Pfeiffer, M.D.
principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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