Recruiting

Phase 2

NK Cell TherapyPersonalized NK Cell Therapy in CBT

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT02727803

Conditions

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

Eligibility Criteria

Sex: All

Age: 15 - 70+

Healthy Volunteers: Not accepted

Interventions

Allogeneic Natural Killer Cell Line NK-92

Anti-Thymocyte Globulin

Busulfan

Clofarabine

Cyclophosphamide

Study Details

Brief summary:

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.

Conditions

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

Study ID

NCT02727803

Start date

May 19, 2016

Status verified date

May, 2026

Completion date

May 31, 2027

Anticipated

Primary completion date

May 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 15 - 70+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

100 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

Interventions

Allogeneic Natural Killer Cell Line NK-92

Given IV

Anti-Thymocyte Globulin

Given IV

Busulfan

Given IV

Clofarabine

Given IV

Cyclophosphamide

Given IV

Fludarabine Phosphate

Given IV

Laboratory Biomarker Analysis

Correlative studies

Melphalan

Given IV

Rituximab

Given IV

Total-Body Irradiation

Undergo total body irradiation

Umbilical Cord Blood Transplantation

Undergo umbilical cord blood transplantation

Primary outcome measure

Progression free survival (PFS) time in C2C2 patients [ Time Frame: From the date of engraftment to disease progression or death, assessed up to 4 years ]
Progression free survival (PFS) time in C1 patients [ Time Frame: From the date of cord blood transplant to disease progression or death, assessed up to 4 years ]

Central Contacts and Locations

Central contacts

Warren B Fingrut, MD

WBFingrut@mdanderson.org

Locations

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Warren B Fingrut, MD

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Jul 30, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-07-30.