Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies
Condition: B-Lymphoid Malignancies; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Non-hodgkin Lymphoma
MeSH terms: Leukemia; Neoplasms; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      If you are reading and signing this form on behalf of a potential participant, please note:
      Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
      participant.

      The goal of this clinical research study is to learn if giving genetically changed immune
      cells, called CAR-NK cells, after chemotherapy will improve the disease in stem cell
      transplant patients with relapsed (has returned) and/or refractory (has not responded to
      treatment) B-cell lymphoma or leukemia. Also, researchers want to find the highest tolerable
      dose of CAR-NK cells to give to patients with relapsed or refractory B-cell lymphoma or
      leukemia. The safety of this treatment will also be studied.

      This is an investigational study. The making of and infusion of genetically changed NK cells
      and the drug AP1903 (if you receive it, explained below) are not FDA approved or commercially
      available for use in this type of disease. They are currently being used for research
      purposes only. The chemotherapy drugs in this study (fludarabine, cyclophosphamide, and
      mesna) are commercially available and FDA approved.

      Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.
    

Detailed description: 
      Objectives:

      Primary objective:

      To determine the safety and relative efficacy of Chimeric antigen receptors
      (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells in
      patients with relapsed/refractory CD19+ B lymphoid malignancies.

      Secondary Objectives:

        1. To assess the overall response rate (complete and partial response rates).

        2. To quantify persistence of infused allogeneic donor CAR-transduced CB-derived NK cells
           in the recipient.

        3. To conduct comprehensive immune reconstitution studies.
    

Intervention name(s): Fludarabine; Cyclophosphamide; Mesna; iC9/CAR.19/IL15-Transduced CB-NK Cells; AP1903
Intervention type(s): Drug; Drug; Drug; Biological; Drug
Intervention description(s): 30 mg/m2 by vein on Days -5 to -3.; 300 mg/m2 by vein on Days -5 to -3.; 300 mg/m2 by vein on Days -5 to -3 before and after the cyclophosphamide dose.; Infusion of iC9/CAR.19/IL15-transduced CB-NK cells on Day 0 by vein.
Starting dose: 10E5; If participant has graft-versus-host disease (GvHD) or cytokine release syndrome after the NK cell infusion, they will receive AP1903 0.4 mg/kg administered as an intravenous infusion.
Other intervention name(s): Fludarabine phosphate; Fludara; Cytoxan; Neosar; Mesnex; NK cells
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: B-Lymphoid Malignancies; Relapsed/Refractory; Acute lymphocytic leukemia; ALL; Chronic lymphocytic leukemia; CLL; Non-Hodgkin lymphoma; NHL; (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer cells; CB-NK cells; Fludarabine; Fludarabine phosphate; Fludara; Cyclophosphamide; Cytoxan; Neosar; AP1903; Mesna; Mesnex