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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT02727803

Personalized NK Cell Therapy in CBT

A Phase 2 study testing Allogeneic Natural Killer Cell Line NK-92, Anti-Thymocyte Globulin and Busulfan in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Biphenotypic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

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Trial 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. Read more about this study

Who is it for?
Ages 15 to 80 years
What is being tested?
Allogeneic Natural Killer Cell Line NK-92, Anti-Thymocyte Globulin and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteUnited States
Study dates
19 May 2016to 31 May 2027
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Warren B Fingrut, MD contact

WBFingrut@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Warren B Fingrut, MD

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Progression-free survival (PFS) time.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Allogeneic Natural Killer Cell Line NK-92, Anti-Thymocyte Globulin, Busulfan, Clofarabine, Cyclophosphamide
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Chronic-Phase, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Myelodysplastic-Myeloproliferative Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Natural Killer Cell Line NK-92Biological

    Also called haNK, NK-92, NK-92 Cells

    Given IV

  • Anti-Thymocyte GlobulinBiological

    Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATS

    Given IV

  • BusulfanDrug

    Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum

    Given IV

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation

    Undergo total body irradiation

  • Umbilical Cord Blood TransplantationProcedure or surgery

    Also called Cord Blood Transplantation, UCB transplantation

    Undergo umbilical cord blood transplantation

Study groups in NCT02727803
Study groupRoleWhat they receive
Myeloablative regimen 1ExperimentalPatients 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.
Receives: Biological: Allogeneic Natural Killer Cell Line NK-92; Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Clofarabine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation
Non-myeloablative regimen 2ExperimentalPatients 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.
Receives: Biological: Allogeneic Natural Killer Cell Line NK-92; Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Rituximab; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation
Reduced intensity regimen 3ExperimentalPatients 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.
Receives: Biological: Allogeneic Natural Killer Cell Line NK-92; Biological: Anti-Thymocyte Globulin; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Procedure: Umbilical Cord Blood Transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS) time in C2C2 patients

    Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, human leukocyte antigen (HLA) match, cytomegalovirus (CMV) status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: From the date of engraftment to disease progression or death, assessed up to 4 years

  2. Progression free survival (PFS) time in C1 patients

    Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: From the date of cord blood transplant to disease progression or death, assessed up to 4 years

Secondary outcomes (4)

  1. Overall survival time

    Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: Up to 4 years

  2. Incidence of transplant related mortality

    Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: Up to 4 years

  3. Incidence of graft-versus host disease

    Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: Up to 4 years

  4. Incidence of infection

    Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2016 (estimated)
  2. Study start19 May 2016
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02727803
Sponsor's protocol ID
2015-0313
Other IDs
NCI-2016-00584, 2015-0313, R01CA211044
Status last verified
May 2026
First submitted
25 Mar 2016
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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