Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia With Gene Mutations, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Therapy-Related Acute Myeloid Leukemia
Conditions
Brief summary
This phase I/II studies the side effects and best dose of natural killer cells before and after donor stem cell transplant and to see how well they work in treating patients with acute myeloid leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia. Giving chemotherapy with or without total body irradiation before a donor peripheral blood stem cell or bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate safety, tolerability and identify the maximum tolerated dose (MTD) of expanded natural killer (NK) cells to be used in patients with myeloid malignancies undergoing a haploidentical stem-cell transplant. SECONDARY OBJECTIVES: I. To determine survival of NK cells in vivo post-transplant. II. To determine the function of NK cells post-transplant and compare with a retrospective control treated with no NK cells. III. To estimate the proportion of patients with engraftment/graft failure. IV. To estimate the non-relapse mortality (NRM) at day 100 post-transplant. V. To estimate the cumulative incidence of grade III-IV aGVHD (acute graft-versus-host disease) at day 100. VI. To assess the rate of chronic graft-versus-host disease (GVHD) within the first year post transplantation. VII. To assess immune reconstitution post-transplant. VIII. To assess disease response, disease-free survival (DFS) and overall survival (OS) after transplantation. IX. To perform a retrospective comparison of patients treated on the study with NK cells will be performed with a Center for International Blood and Marrow Transplant Research (CIBMTR) control of similar patients who did not receive NK cells. OUTLINE: This is a phase I, dose-escalation study of NK cells followed by a phase II study. Patients are assigned to 1 of 2 conditioning regimens. MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo total-body irradiation (TBI) on day -3, and NK cells IV over 30 minutes on day -2 or -1. NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow transplant on day 0. POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then orally (PO) for approximately 4 months, and mycophenolate mofetil PO thrice daily (TID) beginning on day 5 for approximately 6-7 months. NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. After completion of study treatment, patients are followed up for 2 years.
Interventions
PROCEDUREAllogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSC or bone marrow transplant
PROCEDUREBone Marrow Transplantation
Undergo allogeneic PBSC or bone marrow transplant
DRUGCyclophosphamide
Given IV
DRUGFludarabine
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGMelphalan
Given IV
DRUGMycophenolate Mofetil
Given PO
BIOLOGICALNatural Killer Cell Therapy
Given IV
PROCEDUREPeripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSC or bone marrow transplant
DRUGTacrolimus
Given IV and PO
RADIATIONTotal-Body Irradiation
Undergo TBI
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age 2-17 years old may be enrolled after at least 4 adults (ages 18-65 years old) have been treated without toxicity * Patient with no matched related donor who has a related haploidentical donor identified (=\< 7/8 allele match at the A, B, C, DR loci) who is willing to undergo a bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's admission for transplant; the donor must be 16 years of age or older and weigh at least 110 pounds * Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as: (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g. DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (\> 3 abnormalities); (vi) treatment-related AML, or b. second or greater remission; patients beyond second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction * Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy, or b. patients with treatment-related MDS * Chronic myeloid leukemia (CML): a. failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b. accelerated phase or blast phase at any time * Performance score of at least 70% by Karnofsky or 0 to 1 by Eastern Cooperative Oncology Group (ECOG) (age \>= 12 years), or Lansky Play-performance scale of at least 70% or greater (age \< 12 years) * Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-Gault formula) * Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or less than 200 IU/ml for adults * Conjugated (direct) bilirubin less than 2 x upper limit of normal * Left ventricular ejection fraction equal or greater than 40% * Diffusing capacity of the lung for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin; for children =\< 7 years of age who are unable to perform pulmonary function tests (PFT), oxygen saturation \>= 92% on room air by pulse oximetry * Patient or patient's legal representative, parent(s) or guardian should provide written informed consent; assent of a minor if participant's age is at least seven and less than eighteen years
Exclusion criteria
* Human immunodeficiency virus (HIV) positive; active hepatitis B or C * Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion * Liver cirrhosis * Central nervous system (CNS) involvement within 3 months * Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization * Inability to comply with medical therapy or follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to day 70 post-transplant | Number of participants that experienced dose limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 100-day Treatment Related Mortality | Up to 100 days post-transplant | Number of participants who died within 100 days post-transplant. |
| Overall Survival | Up to 2 years | Number of participants with overall survival after 2 years. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at MD Anderson Cancer Center from April 2014 until June 2019.
Pre-assignment details
Total number of participants registered in MDACC was 54, which 27 participants were Donors (Signed consent but not involved in results outcome and no Adverse events were collected) and 27 were Recipients (Treated with donor NK cells).
Participants by arm
| Arm | Count |
|---|---|
| Phase I: NK Cell Dose Level 1_10^4 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8 Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 1 |
| Phase I: NK Cell Dose Level 2_10^5 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8 Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 2 |
| Phase I: NK Cell Dose Level 3_10^6 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8 Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 3 |
| Phase I: NK Cell Dose Level 4_ 10^7 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8 Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 3 |
| Phase I: NK Cell Dose Level 5_3x10^7 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8 Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 2 |
| Phase I: NK Cell Dose Level 6_10^8 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90. Cohort 1: 1xE4 Cohort 2: 1xE5 Cohort 3: 1xE6 Cohort 4: 1xE7 Cohort 5: 3xE7 Cohort 6: 1xE8
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 3 |
| Phase II: NK Cell Dose Level 5_3x10^7 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90.
Cohort 5: 3xE7 Cohort 6: 1xE8
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 3 |
| Phase II: NK Cell Dose Level 6_10^8 MYELOABLATIVE CONDITIONING REGIMEN: Patients receive high-dose melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and NK cells IV over 30 minutes on day -2 or -1.
NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive melphalan IV over 30 minutes on day -7, fludarabine IV over 1 hour on days -7 to -4, undergo TBI on day -3, and receive NK cells IV over 30 minutes on day -2 or -1.
TRANSPLANT: Patients undergo allogeneic PBSC or bone marrow transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO TID beginning on day 5 for approximately 6-7 months.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28-90.
Cohort 5: 3xE7 Cohort 6: 1xE8
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Cyclophosphamide: Given IV Fludarabine: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Natural Killer Cell Therapy: Given IV Peripheral Blood Stem Cell Transplantation: Undergo allogeneic PBSC or BMT Tacrolimus: Given IV and PO Total-Body Irradiation: Undergo TBI | 10 |
| Donor KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase I: NK Cell Dose Level 1_10^4 | Phase I: NK Cell Dose Level 2_10^5 | Phase I: NK Cell Dose Level 3_10^6 | Phase I: NK Cell Dose Level 4_ 10^7 | Phase I: NK Cell Dose Level 5_3x10^7 | Phase I: NK Cell Dose Level 6_10^8 | Phase II: NK Cell Dose Level 5_3x10^7 | Phase II: NK Cell Dose Level 6_10^8 | Donor | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 10 Participants | 24 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants | 24 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Iran | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 2 participants | 3 participants | 3 participants | 2 participants | 2 participants | 3 participants | 10 participants | 27 participants | 53 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 5 Participants | 16 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 2 | 1 / 3 | 0 / 3 | 0 / 2 | 0 / 2 | 1 / 3 | 5 / 10 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 2 / 2 | 3 / 3 | 3 / 3 | 2 / 2 | 2 / 2 | 3 / 3 | 10 / 10 | 0 / 0 |
| serious Total, serious adverse events | 1 / 1 | 0 / 2 | 3 / 3 | 0 / 3 | 0 / 2 | 0 / 2 | 2 / 3 | 6 / 10 | 0 / 0 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants that experienced dose limiting toxicities.
Time frame: Up to day 70 post-transplant
Population: Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: NK Cell Dose Level 1_10^4 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase I: NK Cell Dose Level 2_10^5 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase I: NK Cell Dose Level 3_10^6 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase I: NK Cell Dose Level 4_ 10^7 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase I: NK Cell Dose Level 5_3x10^7 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase I: NK Cell Dose Level 6_10^8 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase II: NK Cell Dose Level 5_3x10^7 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase II: NK Cell Dose Level 6_10^8 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Donor | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
100-day Treatment Related Mortality
Number of participants who died within 100 days post-transplant.
Time frame: Up to 100 days post-transplant
Population: Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: NK Cell Dose Level 1_10^4 | 100-day Treatment Related Mortality | 1 Participants |
| Phase I: NK Cell Dose Level 2_10^5 | 100-day Treatment Related Mortality | 0 Participants |
| Phase I: NK Cell Dose Level 3_10^6 | 100-day Treatment Related Mortality | 0 Participants |
| Phase I: NK Cell Dose Level 4_ 10^7 | 100-day Treatment Related Mortality | 0 Participants |
| Phase I: NK Cell Dose Level 5_3x10^7 | 100-day Treatment Related Mortality | 0 Participants |
| Phase I: NK Cell Dose Level 6_10^8 | 100-day Treatment Related Mortality | 0 Participants |
| Phase II: NK Cell Dose Level 5_3x10^7 | 100-day Treatment Related Mortality | 0 Participants |
| Phase II: NK Cell Dose Level 6_10^8 | 100-day Treatment Related Mortality | 3 Participants |
| Donor | 100-day Treatment Related Mortality | 0 Participants |
Secondary
Overall Survival
Number of participants with overall survival after 2 years.
Time frame: Up to 2 years
Population: Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I: NK Cell Dose Level 1_10^4 | Overall Survival | 1 Participants |
| Phase I: NK Cell Dose Level 2_10^5 | Overall Survival | 1 Participants |
| Phase I: NK Cell Dose Level 3_10^6 | Overall Survival | 1 Participants |
| Phase I: NK Cell Dose Level 4_ 10^7 | Overall Survival | 0 Participants |
| Phase I: NK Cell Dose Level 5_3x10^7 | Overall Survival | 0 Participants |
| Phase I: NK Cell Dose Level 6_10^8 | Overall Survival | 0 Participants |
| Phase II: NK Cell Dose Level 5_3x10^7 | Overall Survival | 1 Participants |
| Phase II: NK Cell Dose Level 6_10^8 | Overall Survival | 5 Participants |
| Donor | Overall Survival | 0 Participants |