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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Day 0 and possible second cycle \> 30 days after the first course
Day -1 and possible second cycle \> 30 days after the first course (Pilot Pediatric/Young Adult Cohort). Day 30 and possible second cycle \>30 days after the first course (Phase 2 Adult Cohort)
On Day -2 or -1
Washington University School of Medicine
St Louis, Missouri, United States
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)
-Feasibility is defined as the ability to generate and successfully infuse CIML NK cells with SOC donor lymphocyte infusion (DLI). Will be considered successful if doses above the minimum can be delivered in at least 18 of 24 patients. Target and minimum CIML doses are maximum capped at 20x10\^6/kg with a minimum dose of 0.5x10\^6 kg.
Time frame: Completion of all recipients through Day 0
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)
Unexpected early mortality is defined as deaths that occur through day 100 that are possibly, probably, or definitely related to the study treatment.
Time frame: Up to Day 100
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)
Unacceptable GVHD is defined as grade IV acute GVHD as assessed by the Minnesota Grading Scale or grade D acute GVHD as assessed by the CIBMTR Grading Scale.
Time frame: From day 14 through month 6
Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Prolonged Neutropenia (Pilot Pediatric/Young Adult Cohort)
Prolonged neutropenia is defined as an absolute neutrophil count \<500/μL persisting for \> 2 weeks.
Time frame: 8 weeks post CIML NK infusion
Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unexpected Early Mortality (Phase 2 Adult Cohort)
Unexpected early mortality is defined as deaths that occur through day 100 that are possibly, probably, or definitely related to the study treatment.
Time frame: Up to Day 100
Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Unacceptable GVHD (Phase 2 Adult Cohort)
Unacceptable GVHD is defined as grade IV acute GVHD as assessed by the Minnesota Grading Scale or grade D acute GVHD as assessed by the CIBMTR Grading Scale.
Time frame: From day 14 through month 6
Safety of Administering CIML NK Cells Plus T Cell DLI as Measured by Number of Recipients With Prolonged Neutropenia (Phase 2 Adult Cohort)
Prolonged neutropenia is defined as an absolute neutrophil count \<500/μL persisting for \> 2 weeks.
Time frame: 8 weeks post CIML NK infusion
Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort)
-LFS is defined as the time from achievement of CR/CRi to the time of relapse, death in remission, or last follow-up.
Time frame: 6 months
Complete Remission Rate (CR/CRi) (Pilot Pediatric/Young Adult Cohort)
* Complete remission (CR):Morphologically leukemia free state (i.e. bone marrow with \<5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL. Patient must be independent of transfusions * Complete remission with incomplete blood count recover (CRi): All of the above criteria for CR must be met, except that absolute neutrophils \<1000 /μL or platelets \<100,000 /μL in the blood.
Time frame: Day 30
Complete Remission Rate (CR/CRi) (Phase 2 Adult Cohort)
* Complete remission (CR):Morphologically leukemia free state (i.e. bone marrow with \<5% blasts by morphologic criteria and no blasts with Auer rods, no evidence of extramedullary leukemia) and absolute neutrophil count ≥1000 /μL and platelets ≥100,000 /μL. Patient must be independent of transfusions * Complete remission with incomplete blood count recover (CRi): All of the above criteria for CR must be met, except that absolute neutrophils \<1000 /μL or platelets \<100,000 /μL in the blood.
Time frame: Day 30
Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Pilot Pediatric/Young Adult Cohort)
-LFS is defined as the time from achievement of CR/CRi to the time of relapse, death in remission, or last follow-up.
Time frame: 100 days post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Pilot Pediatric/Young Adult Cohort)
-LFS is defined as the time from achievement of CR/CRi to the time of relapse, death in remission, or last follow-up.
Time frame: 1 year post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort)
-LFS is defined as the time from achievement of CR/CRi to the time of relapse, death in remission, or last follow-up.
Time frame: 100 days post CIML NK cell infusion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Kaplan-Meier Estimate of Percentage of Participants With Leukemia-Free Survival (LFS) (Phase 2 Adult Cohort)
-LFS is defined as the time from achievement of CR/CRi to the time of relapse, death in remission, or last follow-up.
Time frame: 1 year post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Pilot Pediatric/Young Adult Cohort)
-OS is defined as the time from the date of Day 0 until death from any cause.
Time frame: 100 days post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Pilot Pediatric/Young Adult Cohort)
-OS is defined as the time from the date of Day 0 until death from any cause.
Time frame: 1 year post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Phase 2 Adult Cohort)
-OS is defined as the time from the date of Day 0 until death from any cause.
Time frame: 100 days post CIML NK cell infusion
Kaplan-Meier Estimate of Percentage of Participants With Overall Survival (OS) (Phase 2 Adult Cohort)
-OS is defined as the time from the date of Day 0 until death from any cause.
Time frame: 1 year post CIML NK cell infusion
Incidence and Severity of Acute GVHD Rates as Assessed on the Minnesota Grading Scale (Pilot Pediatric/Young Adult Cohort)
* Incidence and severity of acute GVHD will be assessed based on the Minnesota grading scale. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * The Minnesota Grading scale is graded with I, II, III, IV. Grade I is the least severe and Grade IV is the most severe.
Time frame: Day 14 through 6 months
Incidence and Severity of Acute GVHD Rates as Assessed on the CIBMTR Grading Scale (Pilot Pediatric/Young Adult Cohort)
* Incidence and severity of acute GVHD will be assessed based on the CIBMTR grading scale. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * The CIBMTR grading scale is graded with A, B, C, or D. Grade A is considered the least severe with Grade D being the most severe.
Time frame: Day 14 through 6 months
Incidence and Severity of Chronic GVHD Rates (Pilot Pediatric/Young Adult Cohort)
* Incidence and severity of chronic GVHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * Severity is graded with mild, moderate, or severe chronic GVHD.
Time frame: Day 100 through 12 months
Incidence and Severity of Acute GVHD Rates as Assessed on the Minnesota Grading Scale (Phase 2 Adult Cohort)
* Incidence and severity of acute GVHD will be assessed based on the CIBMTR grading scale. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * The Minnesota Grading scale is graded with I, II, III, IV. Grade I is the least severe and Grade IV is the most severe.
Time frame: Day 14 through 6 months
Incidence and Severity of Acute GVHD Rates as Assessed on the CIBMTR Grading Scale (Phase 2 Adult Cohort)
* Incidence and severity of acute GVHD will be assessed based on the CIBMTR grading scale. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * The CIBMTR grading scale is graded with A, B, C, or D. Grade A is considered the least severe with Grade D being the most severe.
Time frame: Day 14 through 6 months
Incidence and Severity of Chronic GVHD Rates (Phase 2 Adult Cohort)
* Incidence and severity of chronic GVHD will be assessed based on the NIH consensus criteria and global severity scoring system. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s). * Severity is graded with mild, moderate, or severe chronic GVHD.
Time frame: Day 100 through 12 months