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Personalized NK Cell Therapy in CBT

ConditionsAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveAcute Biphenotypic LeukemiaAcute Lymphoblastic LeukemiaAcute Lymphoblastic Leukemia in RemissionAcute Myeloid Leukemia With Myelodysplasia-Related ChangesAcute Myeloid Leukemia With Variant MLL TranslocationsB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Chemotherapy-Related LeukemiaChronic Myelomonocytic LeukemiaChronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveHigh Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsISS Stage II Plasma Cell MyelomaISS Stage III Plasma Cell MyelomaMyelodysplastic SyndromeMyelodysplastic Syndrome With Excess BlastsMyelodysplastic Syndrome With Gene MutationMyelodysplastic/Myeloproliferative NeoplasmPreviously Treated Myelodysplastic SyndromeRecurrent Acute Myeloid LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Hodgkin LymphomaRecurrent Non-Hodgkin LymphomaRefractory Acute Lymphoblastic LeukemiaRefractory Adult Acute Lymphoblastic LeukemiaSecondary Acute Myeloid LeukemiaTherapy-Related Myelodysplastic Syndrome
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age15-80
SponsorM.D. Anderson Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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 design

Design model

Parallel

Treatments tested in this trial

  • Allogeneic Natural Killer Cell Line NK-92

    Biological/Vaccine

    Given IV

  • Anti-Thymocyte Globulin

    Biological/Vaccine

    Given IV

  • Busulfan

    Drug

    Given IV

  • Clofarabine

    Drug

    Given IV

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine Phosphate

    Drug

    Given IV

  • Laboratory Biomarker Analysis

    Other intervention

    Correlative studies

  • Melphalan

    Drug

    Given IV

  • Rituximab

    Biological/Vaccine

    Given IV

  • Total-Body Irradiation

    Radiation

    Undergo total body irradiation

  • Umbilical Cord Blood Transplantation

    Procedure/Surgery

    Undergo umbilical cord blood transplantation

Treatment groups

100 Participants
are divided into 3 treatment groups
Group A: Myeloablative regimen 1Experimental treatment 8 interventions
Group B: Non-myeloablative regimen 2Experimental treatment 8 interventions
Group C: Reduced intensity regimen 3Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

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.

Time frame
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.

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

Secondary outcomes

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.

Time frame
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.

Time frame
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.

Time frame
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.

Time frame
Up to 4 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

M.D. Anderson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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