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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
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.
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Number of Events That Was Grade 3-4 Toxicities
Toxicity is defined as a grade 3 or 4 within 40 days of NK cell infusion.
Time frame: 40 days
Overall Response Rate of Participants Analyzed
Participants response was defined as partial or complete response by Efftox assessment below. * Acute lymphoblastic leukemia: Complete response will be defined as bone marrow with \< 5% blasts, the absence of circulating blasts, and no extramedullary sites of disease (as assessed by means of computed tomography or positron-emission tomography), regardless of cell-count recovery. * CLL: Response will be defined based on the NCI-WG/IWCLL 2008 criteria, Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia. Lymphomas: Response will be defined based on the Lugano criteria- Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma:
Time frame: 30 days
Number of Participants Achieved an Objective Response
Number of participants that had Complete and Partial Response.
Time frame: Up to 100 days after NK cell infusion
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