Natural Killer Cells Before and After Donor Stem Cell Tra... | NCT01904136

ID	Type	Description	Link
NCI-2013-02183	Registry Identifier	CTRP (Clinical Trial Reporting Program)
P01 - 5P01
RP110553 05-07-04832
05-07-04832
2012-0708	Other Identifier	M D Anderson Cancer Center
P01CA049639	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

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.

Label	Type	Description	Intervention Names
Treatment (NK cells, allogeneic stem cell transplant)	Experimental	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.	Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Bone Marrow Transplantation Drug: Cyclophosphamide Drug: Fludarabine Other: Laboratory Biomarker Analysis Drug: Melphalan Drug: Mycophenolate Mofetil Biological: Natural Killer Cell Therapy Procedure: Peripheral Blood Stem Cell Transplantation Drug: Tacrolimus Radiation: Total-Body Irradiation

Name	Type	Description	Arm Group Labels	Other Names
Allogeneic Hematopoietic Stem Cell Transplantation	Procedure	Undergo allogeneic PBSC or bone marrow transplant	Treatment (NK cells, allogeneic stem cell transplant)

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	Number of participants that experienced dose limiting toxicities.	Up to day 70 post-transplant

Measure	Description	Time Frame
100-day Treatment Related Mortality	Number of participants who died within 100 days post-transplant.	Up to 100 days post-transplant
Overall Survival	Number of participants with overall survival after 2 years.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Samer Srour	M.D. Anderson Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
M D Anderson Cancer Center		Houston	Texas	77030	United States

PubMed Identifier	Type	Citation	Retractions
34312462	Derived	Ciurea SO, Kongtim P, Soebbing D, Trikha P, Behbehani G, Rondon G, Olson A, Bashir Q, Gulbis AM, Indreshpal K, Rezvani K, Shpall EJ, Bassett R, Cao K, Martin AS, Devine S, Horowitz M, Pasquini M, Lee DA, Champlin RE. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022 Jan;36(1):155-164. doi: 10.1038/s41375-021-01349-4. Epub 2021 Jul 26.

ID	Title	Description
FG000	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

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 14, 2020

Arm/Group Information

ID	Title	Description
BG000	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
BG001	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
BG002	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
BG003	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
BG004	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
BG005	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
BG006	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
BG007	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
BG008	Donor	KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.
BG009	Total	Total of all reporting groups

Units	Counts
Participants	BG0001 BG0012 BG0023 BG0033 BG0042 BG0053 BG0063 BG00710 BG00827 BG00954

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Primary

Number of Participants With Dose Limiting Toxicities (DLTs)

Number of participants that experienced dose limiting toxicities.

Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.

Posted

Count of Participants

Participants

Up to day 70 post-transplant

ID	Title	Description
OG000	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
OG001	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
OG002	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
OG003	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
OG004	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
OG005	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
OG006	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
OG007	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
OG008	Donor	KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.

Units	Counts
Participants	OG0001 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

100-day Treatment Related Mortality

Number of participants who died within 100 days post-transplant.

Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.

Posted

Count of Participants

Participants

Up to 100 days post-transplant

ID	Title	Description
OG000	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

Secondary

Overall Survival

Number of participants with overall survival after 2 years.

Twenty seven donor participants only signed consents and were not part of the results outcome and Adverse events were not collected.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	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

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	1	1	1	1	1
EG001	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	1	2	0	2	2	2
EG002	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	1	3	3	3	3	3
EG003	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	0	3	0	3	3	3
EG004	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	0	2	0	2	2	2
EG005	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	0	2	0	2	2	2
EG006	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	1	3	2	3	3	3
EG007	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	5	10	6	10	10	10
EG008	Donor	KIR mismatched haplo donors, KIR mismatched cord blood donors or HLA matched related donors.	0	0	0	0	0	0

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bacterial Infections	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0011 affected2 at risk EG0023 affected3 at risk EG0032 affected3 at risk EG0042 affected2 at risk EG0051 affected2 at risk EG0062 affected3 at risk EG0075 affected10 at risk EG0080 affected0 at risk
Flu like syndrome	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Neutropenic fevers	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0011 affected2 at risk EG0021 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0011 affected2 at risk EG0022 affected3 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0011 affected2 at risk EG0023 affected3 at risk EG003
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Viral Infections	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0023 affected3 at risk EG003
Fevers	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Fluid overload	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0022 affected3 at risk EG003
Skin GvHD	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0021 affected3 at risk EG003
GI GvHD	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Elevated bilirubin	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0011 affected2 at risk EG0021 affected3 at risk EG003
Fungal Infections	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
HSCT related microangiopathy (TA-TMA)	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0022 affected3 at risk EG003
Liver GvHD	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Upper GI GvHD	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hemorrhagic Cystitis	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Headache	Nervous system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Mucositis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
BK virus associated hemorrhagic cystitis	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Elevated transminitis	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Neutropenic enterocolitis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Cytoxan induced Hemorrhagic Cystitis	Renal and urinary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Creatinine increased	Investigations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003

ID	Term
D015465	Leukemia, Myeloid, Accelerated Phase
D001752	Blast Crisis
D009190	Myelodysplastic Syndromes
D015470	Leukemia, Myeloid, Acute
D015464	Leukemia, Myelogenous, Chronic, BCR-ABL Positive

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D002471	Cell Transformation, Neoplastic
D063646	Carcinogenesis
D009385	Neoplastic Processes

ID	Term
D033581	Stem Cell Transplantation
D016026	Bone Marrow Transplantation
D001800	Blood Specimen Collection
D003520	Cyclophosphamide
C024352	fludarabine
D008558	Melphalan
D009173	Mycophenolic Acid
D036102	Peripheral Blood Stem Cell Transplantation
D016559	Tacrolimus
D014916	Whole-Body Irradiation

ID	Term
D017690	Cell Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D013812	Therapeutics
D014180	Transplantation
D013514	Surgical Procedures, Operative
D016378	Tissue Transplantation
D013048	Specimen Handling
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis
D011677	Punctures
D008919	Investigative Techniques
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D010649	Phenylalanine
D024322	Amino Acids, Aromatic
D000598	Amino Acids, Cyclic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005227	Fatty Acids
D008055	Lipids
D018380	Hematopoietic Stem Cell Transplantation
D018942	Macrolides
D007783	Lactones
D011878	Radiotherapy

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Secondary graft failure	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG0030 affected3 at risk EG004
Viral Infections	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0001 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Bacterial Infections	Infections and infestations	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
GI GvHD	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Delayed engraftment	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Liver GvHD	Hepatobiliary disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
CNS hemorrahge due to DSA/PLT Refractory	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected1 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003