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

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ClinicalTrials.gov Identifier: NCT02727803
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Adult Acute Myeloid Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Refractory Adult Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia Secondary Acute Myeloid Leukemia Therapy-Related Myelodysplastic Syndrome Biological: Allogeneic Natural Killer Cell Line NK-92 Biological: Anti-Thymocyte Globulin Drug: Busulfan Drug: Clofarabine Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Melphalan Biological: Rituximab Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Phase 2

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : May 19, 2020
Estimated Study Completion Date : May 19, 2020


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
  • ATGAM
  • ATS
  • Thymoglobulin

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
  • ATGAM
  • ATS
  • Thymoglobulin

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
  • RTXM83

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
  • ATGAM
  • ATS
  • Thymoglobulin

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




Primary Outcome Measures :
  1. 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 ]
    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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02727803


Contacts
Layout table for location contacts
Contact: Katy Rezvani 713-792-8750 krezvani@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Katy Rezvani    713-792-8750      
Principal Investigator: Katy Rezvani         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Katy Rezvani M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02727803     History of Changes
Other Study ID Numbers: 2015-0313
NCI-2016-00584 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0313 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
R01CA211044 ( U.S. NIH Grant/Contract )
First Posted: April 5, 2016    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Blood Protein Disorders
Lymphoma
Syndrome
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myeloproliferative Disorders
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Accelerated Phase
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Biphenotypic, Acute
Anemia, Refractory, with Excess of Blasts
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases