Phase 2
N=62
Cytokine Induced Memory-like NK Cell Adoptive Therapy for Relapsed AML After Allogeneic Hematopoietic Cell Transplant
Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT03068819 ↗Enrolled (actual)
62
Serious AEs
24.2%
Results posted
Apr 2026
Primary outcome: Primary: Feasibility of Successfully Generating CIML NK Cells With Standard of Care (SOC) DLI From the Original Stem Cell Donor as Measured by the Number of Participants That Had Successful Doses Infused (Pilot Pediatric/Young Adult Cohort) — 18 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- CIML NK Cell Infusion (Drug); CD3+ T Cell Product Infusion (Procedure); Leukapheresis (Procedure)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Washington University School of Medicine
- Primary completion
- Jun 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Feasibility of Successfully Generating CIML NK Cells With Standard of Care (SOC) DLI From the Original Stem Cell Donor as Measured by the Number of Participants That Had Successful Doses Infused (Pilot Pediatric/Young Adult Cohort) |
18 | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unexpected Early Mortality (Pilot Pediatric/Young Adult Cohort) |
— | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unacceptable Graft Versus Host Disease (GVHD) (Pilot Pediatric/Young Adult Cohort) |
— | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Prolonged Neutropenia (Pilot Pediatric/Young Adult Cohort) |
— | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unexpected Early Mortality (Phase 2 Adult Cohort) |
1 | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unacceptable GVHD (Phase 2 Adult Cohort) |
1 | — |
| PRIMARY Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Prolonged Neutropenia (Phase 2 Adult Cohort) |
— | — |
| PRIMARY Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort) |
20.000 | — |
| SECONDARY Complete Remission Rate (CR/CRi) (Pilot Pediatric/Young Adult Cohort) |
8 | — |
| SECONDARY Complete Remission Rate (CR/CRi) (Phase 2 Adult Cohort) |
5 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Pilot Pediatric/Young Adult Cohort) |
28.571 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Pilot Pediatric/Young Adult Cohort) |
28.571 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort) |
20.000 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort) |
20.000 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Pilot Pediatric/Young Adult Cohort) |
33.333 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Pilot Pediatric/Young Adult Cohort) |
33.333 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Phase 2 Adult Cohort) |
7.143 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Phase 2 Adult Cohort) |
7.143 | — |
| SECONDARY Incidence and Severity of Acute GVHD Rates as Assessed on the Minnesota Grading Scale (Pilot Pediatric/Young Adult Cohort) |
16; 0; 1; 1; 0 | — |
| SECONDARY Incidence and Severity of Acute GVHD Rates as Assessed on the CIBMTR Grading Scale (Pilot Pediatric/Young Adult Cohort) |
16; 0; 1; 1; 0 | — |
| SECONDARY Incidence and Severity of Chronic GVHD Rates (Pilot Pediatric/Young Adult Cohort) |
9; 0; 1; 0 | — |
| SECONDARY Incidence and Severity of Acute GVHD Rates as Assessed on the Minnesota Grading Scale (Phase 2 Adult Cohort) |
11; 0; 1; 1; 1 | — |
| SECONDARY Incidence and Severity of Acute GVHD Rates as Assessed on the CIBMTR Grading Scale (Phase 2 Adult Cohort) |
11; 0; 0; 2; 1 | — |
| SECONDARY Incidence and Severity of Chronic GVHD Rates (Phase 2 Adult Cohort) |
1; 0; 0; 0 | — |
Summary
Donor Lymphocyte Infusion (DLI) following salvage chemotherapy is the one of the most widely used treatment approaches in patients who relapse after allogeneic hematopoietic cell transplant (allo-HCT). However, the complete remission (CR) rates and long term survival remain very poor in these patients and, therefore, there is an unmet need to develop more effective treatment approaches in patients who relapse after allo-HCT.
Based on the initial promising results with our ongoing cytokine-induced memory-like (CIML) natural killer (NK) cell trial, the investigators hypothesize that combining the CIML NK cells with DLI approach will significantly enhance the graft versus leukemia and therefore potentially provide potentially curative therapy for these patients with otherwise extremely poor prognosis. Combining CIML NK cells with the DLI platform will also potentially allow these adoptively transferred cells to persist for longer duration as they should not be rejected by donor T cells as the CIML NK cells are derived from the same donor. The use of CIML NK cells is unlikely to lead to excessive graft versus host disease (GVHD) as previous studies have not been associated with excessive GVHD rates.
Eligibility Criteria
Recipient Inclusion Criteria:
- Relapsed AML after HLA-matched related or unrelated allogeneic hematopoietic cell transplant
- For pilot pediatric/young adult patient cohort ≥1 and 60 %
- Adequate organ function as defined below:
- Total bilirubin 60 mL/min/1.73 m2 by Cockcroft-Gault Formula
- Oxygen saturation ≥90% on room air
- Not currently requiring systemic corticosteroid therapy (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) or any other immune suppressive medications
- Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study including throughout the initial evaluation period (100 days after CIML NK cell infusion).
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Recipient Exclusion Criteria:
- Acute or chronic GvHD with ongoing active systemic treatment.
- Circulating blast count >10, 000/uL by morphology or flow cytometry (cyto-reductive therapies, including salvage chemotherapy, is encouraged prior to study enrollment)
- Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B, or Hepatitis C infection.
- Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
- New or progressive pulmonary infiltrates concerning for new or uncontrolled infectious process.
- Known hypersensitivity to one or more of the study agents
- Received any investigational drugs within the 14 days prior to CIML NK cell infusion date
- Pregnant and/or breastfeeding
Donor Inclusion Criteria:
- At least 18 years of age
- Same donor as used for the allo-HCT
- In general good health, and medically able to tolerate leukapheresis
- Ability to understand and willingness to sign an IRB approved written informed consent document
Donor Exclusion Criteria:
- Active hepatitis, positive for HTLV, or HIV on donor viral screen
- Pregnant
Data sourced from ClinicalTrials.gov (NCT03068819). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.