Personalized NK Cell Therapy in CBT

NCT ID: NCT02727803

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-19

Study Completion Date

2027-05-31

Brief Summary

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This phase II clinical trial studies how well personalized natural killer (NK) cell therapy works after chemotherapy and umbilical cord blood transplant in treating patients with myelodysplastic syndrome, leukemia, lymphoma or multiple myeloma. This clinical trial will test cord blood (CB) selection for human leukocyte antigen (HLA)-C1/x recipients based on HLA-killer-cell immunoglobulin-like receptor (KIR) typing, and adoptive therapy with CB-derived NK cells for HLA-C2/C2 patients. Natural killer cells may kill tumor cells that remain in the body after chemotherapy treatment and lessen the risk of graft versus host disease after cord blood transplant.

Detailed Description

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PRIMARY OBJECTIVES:

I. Progression-free survival (PFS) time.

SECONDARY OBJECTIVES:

I. Overall survival (OS) time. II. Transplant related mortality (TRM). III. Graft versus host disease (GVHD). IV. Infection

OUTLINE: Patients are assigned to 1 of 3 preparative regimens.

MYELOABLATIVE REGIMEN 1: Patients receive anti-thymocyte globulin intravenously (IV) over 4 hours on days -9 and -8, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -7 to -4. Patients undergo total body irradiation (TBI) on day -3.

NON-MYELOABLATIVE REGIMEN 2: Patients with cluster of differentiation (CD)20 positive malignancies receive rituximab IV over 6 hours on day -9. Patients receive anti-thymocyte globulin IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 1 hour on days -6 to -3, and cyclophosphamide IV over 3 hours on day -6 and undergo TBI on day -1 at the discretion of the investigator(s).

REDUCED INTENSITY REGIMEN 3: Patients receive anti-thymocyte globulin IV over 4 hours on days -7 and -6, fludarabine phosphate IV over 1 hour on days -5 to -2, and melphalan IV over 30 minutes on day -2.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0.

NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

After completion of study treatment, patients are followed up at 1, 7, 14, 28, 45, 60, and 100 days, and at 6, 9, and 12 months, and then yearly for up to 4 years.

Conditions

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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Biphenotypic Leukemia Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia With Myelodysplasia-Related Changes Acute Myeloid Leukemia With Variant MLL Translocations B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 Chemotherapy-Related Leukemia Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements ISS Stage II Plasma Cell Myeloma ISS Stage III Plasma Cell Myeloma Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Myelodysplastic Syndrome With Gene Mutation Myelodysplastic/Myeloproliferative Neoplasm Previously Treated Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Refractory Acute Lymphoblastic Leukemia Refractory Adult Acute Lymphoblastic Leukemia Secondary Acute Myeloid Leukemia Therapy-Related Myelodysplastic Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Myeloablative regimen 1

Patients receive anti-thymocyte globulin IV over 4 hours on days -9 and -8, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -7 to -4. Patients undergo TBI on day -3.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0.

NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Group Type EXPERIMENTAL

Allogeneic Natural Killer Cell Line NK-92

Intervention Type BIOLOGICAL

Given IV

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Busulfan

Intervention Type DRUG

Given IV

Clofarabine

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Total-Body Irradiation

Intervention Type RADIATION

Undergo total body irradiation

Umbilical Cord Blood Transplantation

Intervention Type PROCEDURE

Undergo umbilical cord blood transplantation

Non-myeloablative regimen 2

Patients with CD20 positive malignancies receive rituximab IV over 6 hours on day -9. Patients receive anti-thymocyte globulin IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 1 hour on days -6 to -3, and cyclophosphamide IV over 3 hours on day -6 and undergo TBI on day -1 at the discretion of the investigator(s).

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0.

NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Group Type EXPERIMENTAL

Allogeneic Natural Killer Cell Line NK-92

Intervention Type BIOLOGICAL

Given IV

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV

Total-Body Irradiation

Intervention Type RADIATION

Undergo total body irradiation

Umbilical Cord Blood Transplantation

Intervention Type PROCEDURE

Undergo umbilical cord blood transplantation

Reduced intensity regimen 3

Patients receive anti-thymocyte globulin IV over 4 hours on days -7 and -6, fludarabine phosphate IV over 1 hour on days -5 to -2, and melphalan IV over 30 minutes on day -2.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0.

NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.

Group Type EXPERIMENTAL

Allogeneic Natural Killer Cell Line NK-92

Intervention Type BIOLOGICAL

Given IV

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Melphalan

Intervention Type DRUG

Given IV

Umbilical Cord Blood Transplantation

Intervention Type PROCEDURE

Undergo umbilical cord blood transplantation

Interventions

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Allogeneic Natural Killer Cell Line NK-92

Given IV

Intervention Type BIOLOGICAL

Anti-Thymocyte Globulin

Given IV

Intervention Type BIOLOGICAL

Busulfan

Given IV

Intervention Type DRUG

Clofarabine

Given IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Melphalan

Given IV

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Total-Body Irradiation

Undergo total body irradiation

Intervention Type RADIATION

Umbilical Cord Blood Transplantation

Undergo umbilical cord blood transplantation

Intervention Type PROCEDURE

Other Intervention Names

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haNK NK-92 NK-92 Cells Antithymocyte Globulin Antithymocyte Serum ATG ATS 1, 4-Bis[methanesulfonoxy]butane BUS Bussulfam Busulfanum Busulfex Busulphan CB 2041 CB-2041 Glyzophrol GT 41 GT-41 Joacamine Methanesulfonic Acid Tetramethylene Ester Methanesulfonic acid, tetramethylene ester Mielucin Misulban Misulfan Mitosan Myeleukon Myeloleukon Myelosan Mylecytan Myleran Sulfabutin Tetramethylene Bis(methanesulfonate) Tetramethylene bis[methanesulfonate] WR-19508 Clofarex Clolar (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine nitrogen mustard Sarcoclorin Sarkolysin WR-19813 ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 rituximab biosimilar TQB2303 rituximab-abbs RTXM83 Truxima Total Body Irradiation Whole-Body Irradiation Cord Blood Transplantation UCB transplantation

Eligibility Criteria

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Inclusion Criteria

* Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abnormal \[abn\]\[3q\], -5/5q-, -7/7q-, abn\[12p\], abn\[17p\], myeloid/lymphoid or mixed-lineage leukemia \[MLL\] gene re-arrangement and t \[6;9\]47, fms related tyrosine kinase 3 \[flt3\] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (MDS), any disease beyond first remission
* Myelodysplastic syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant; these include any of the following categories: 1) revised International Prognostic Scoring System (IPSS) intermediate and high risk groups, 2) malondialdehyde (MDA) with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p)
* Acute lymphoblastic leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
* Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); relapsed double hit lymphomas; patients with options for treatment that are known to be curative are not eligible
* Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy
* Chronic myeloid leukemia (CML) second chronic phase or accelerated phase
* Hodgkin's disease (HD): Induction failures, after first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease
* Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
* A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure
* Patient age criteria: age \>= 15 and =\< 45 years (myeloablative regimen 1; age \>= 15 and =\< 80 years (nonmyeloablative regimen 2) at the discretion of the investigator(s); age \>= 15 and =\< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy may receive reduced intensity regimen 3
* Performance score of at least 60% by Karnofsky
* Left ventricular ejection fraction of at least 40% (myeloablative regimen 1, reduced intensity regimen 3)
* Left ventricular ejection fraction of at least 30% (nonmyeloablative regimen 2)
* Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (myeloablative regimen 1, reduced intensity regimen 3)
* Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or glomerular filtration rate \[GFR\]) \> 40mL/min/1.73 m\^2
* Serum glutamate pyruvate transaminase (SGPT)/bilirubin \< to 2.0 x normal (myeloablative regimen 1), reduced intensity regimen 3; SGPT/bilirubin \< to 4.0 x normal (nonmyeloablative regimen 2)
* Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months
* Patients with options for treatment that are known to be curative are not eligible
* Patients enrolled in this study may be enrolled on other supportive care investigational new drug (IND) studies at the discretion of the principal investigator (PI)

Exclusion Criteria

* Human immunodeficiency virus (HIV) positive; HIV results will be determined by nucleic acid testing
* Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood \[CB\] transplantation is proposed), or psychiatric condition that would limit informed consent
* Active central nervous system (CNS) disease in patient with history of CNS malignancy
* Availability of appropriate, willing, human leukocyte antigen (HLA)-matched related stem cell donor
Minimum Eligible Age

15 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amanda Olson, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Amanda Olson, MD

Role: CONTACT

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

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NCI-2016-00584

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-0313

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA211044

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2015-0313

Identifier Type: -

Identifier Source: org_study_id

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