Personalized NK Cell Therapy After Chemotherapy and Cord Blood Transplant in Treating Patients With Myelodysplastic Syndrome, Leukemia, Lymphoma or Multiple Myeloma

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT02727803
Collaborator
National Cancer Institute (NCI) (NIH)
100
1
3
108.4
0.9

Study Details

Study Description

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.

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Personalized NK Cell Therapy in Cord Blood Transplantation
Actual Study Start Date :
May 19, 2016
Anticipated Primary Completion Date :
May 31, 2025
Anticipated Study Completion Date :
May 31, 2025

Arms and Interventions

Arm Intervention/Treatment
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.

Biological: Allogeneic Natural Killer Cell Line NK-92
Given IV
Other Names:
  • haNK
  • NK-92
  • NK-92 Cells
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATS
  • Drug: Busulfan
    Given IV
    Other Names:
  • 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
  • Drug: Clofarabine
    Given IV
    Other Names:
  • Clofarex
  • Clolar
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Radiation: Total-Body Irradiation
    Undergo total body irradiation
    Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation
  • Procedure: Umbilical Cord Blood Transplantation
    Undergo umbilical cord blood transplantation
    Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
  • 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.

    Biological: Allogeneic Natural Killer Cell Line NK-92
    Given IV
    Other Names:
  • haNK
  • NK-92
  • NK-92 Cells
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATS
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-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
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Biological: Rituximab
    Given IV
    Other Names:
  • 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
  • Radiation: Total-Body Irradiation
    Undergo total body irradiation
    Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation
  • Procedure: Umbilical Cord Blood Transplantation
    Undergo umbilical cord blood transplantation
    Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
  • 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.

    Biological: Allogeneic Natural Killer Cell Line NK-92
    Given IV
    Other Names:
  • haNK
  • NK-92
  • NK-92 Cells
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATS
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Melphalan
    Given IV
    Other Names:
  • 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
  • Procedure: Umbilical Cord Blood Transplantation
    Undergo umbilical cord blood transplantation
    Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
  • Outcome Measures

    Primary Outcome Measures

    1. Progression free survival (PFS) time in C2C2 patients [From the date of engraftment to disease progression or death, assessed up to 4 years]

      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.

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

      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.

    Secondary Outcome Measures

    1. Overall survival time [Up to 4 years]

      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.

    2. Incidence of transplant related mortality [Up to 4 years]

      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.

    3. Incidence of graft-versus host disease [Up to 4 years]

      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.

    4. Incidence of infection [Up to 4 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Amanda Olson, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02727803
    Other Study ID Numbers:
    • 2015-0313
    • NCI-2016-00584
    • 2015-0313
    • P30CA016672
    • R01CA211044
    First Posted:
    Apr 5, 2016
    Last Update Posted:
    Jun 16, 2022
    Last Verified:
    Jun 1, 2022

    Study Results

    No Results Posted as of Jun 16, 2022