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 : June 16, 2022
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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 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 | 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 |
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.
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 31, 2025 |
Estimated Study Completion Date : | May 31, 2025 |

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:
Biological: Anti-Thymocyte Globulin Given IV
Other Names:
Drug: Busulfan Given IV
Other Names:
Drug: Clofarabine Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Radiation: Total-Body Irradiation Undergo total body irradiation
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo umbilical cord blood transplantation
Other Names:
|
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:
Biological: Anti-Thymocyte Globulin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: Rituximab Given IV
Other Names:
Radiation: Total-Body Irradiation Undergo total body irradiation
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo umbilical cord blood transplantation
Other Names:
|
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:
Biological: Anti-Thymocyte Globulin Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Melphalan Given IV
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo umbilical cord blood transplantation
Other Names:
|
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.

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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 |
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

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
Contact: Amanda Olson, MD | alolson@mdanderson.org |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Principal Investigator: Amanda Olson, MD |
Principal Investigator: | Amanda Olson, MD | M.D. Anderson Cancer Center |
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT02727803 |
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: | June 16, 2022 |
Last Verified: | June 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma Leukemia Leukemia, Myeloid Multiple Myeloma Neoplasms, Plasma Cell Leukemia, Myeloid, Acute Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Myeloid, Chronic-Phase Leukemia, Myeloid, Accelerated Phase Leukemia, Biphenotypic, Acute |
Myelodysplastic Syndromes Myeloproliferative Disorders Myelodysplastic-Myeloproliferative Diseases Anemia, Refractory, with Excess of Blasts Syndrome Recurrence Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Pathologic Processes Disease Attributes |