NCT03056339

Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies

Dose Escalation Study Phase I/II of Umbilical Cord Blood-Derived CAR-Engineered NK Cells in Conjunction With Lymphodepleting Chemotherapy in Patients With Relapsed/Refractory B-Lymphoid Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 7 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• B-Lymphoid Malignancies
• Acute Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia
• Non-hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	Fludarabine	30 mg/m2 by vein on Days -5 to -3.
DRUG	Cyclophosphamide	300 mg/m2 by vein on Days -5 to -3.
DRUG	Mesna	300 mg/m2 by vein on Days -5 to -3 before and after the cyclophosphamide dose.
BIOLOGICAL	iC9/CAR.19/IL15-Transduced CB-NK Cells	Infusion of iC9/CAR.19/IL15-transduced CB-NK cells on Day 0 by vein. Starting dose: 10E5
DRUG	AP1903	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.

Timeline

• Start date: 2017-06-21
• Primary completion: 2023-03-06
• Completion: 2023-03-06
• First posted: 2017-02-17
• Last updated: 2024-03-25
• Results posted: 2024-03-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study