CD19-Specific T Cells Post AlloSCT

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title: Donor-Derived Very-Rapid Manufactured CD19-Specific T Cells for Lymphoid Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation

Status Terminated

Clinical Trial Summary

This phase I trial investigates the side effects and best dose of CD19 positive (+) specific CAR-T cells in treating patients with CD19+ lymphoid malignancies, such as acute lymphoblastic leukemia, non-Hodgkin lymphoma, small lymphocytic lymphoma, or chronic lymphocytic lymphoma. Sometimes researchers change the genetic material in the cells of a patient's T cells using a process called gene transfer. Researchers then inject the changed T-cells into the patient's body. Receiving the T-cell infusion may help to control the disease.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety and maximum tolerated dose (MTD) of donor-derived genetically modified, CD19-specific T cells expressing mbIL15 and HER1t using the Rapid Personalized Manufacture (RPM) process (autologous CD19-CD8-CD28-CD3zeta-chimeric antigen receptor [CAR]-mbIL15-HER1t T cells [CD19-mbIL15-CAR-T cells]) administered to patients with CD19+ advanced lymphoid malignancies who have previously received an allogeneic hematopoietic stem cell transplantation (HSCT), including haploidentical HSCT.

SECONDARY OBJECTIVES:

I. To demonstrate the feasibility of the RPM process. II. To determine the incidence and grading of cytokine release syndrome (CRS) and neurotoxicity.

III. To determine persistence of genetically modified T cells. IV. To determine if cetuximab can control numbers of infused T cells. V. To screen for the development of host immune responses against the transgenes (one or more of CAR, mbIL15, HER1t).

VI. To determine cytokine profile of the patient with infused T cells. VII. To demonstrate the homing ability of the infused T cells. VIII. To assess disease response after T-cell infusion. IX. To assess progression-free and overall survival. X. To detect emergence of CD19 negative (neg) malignant B cells.

OUTLINE: This is a dose-escalation study of autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells.

CHEMOTHERAPY: Patients receive fludarabine intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5, -4, and -3 in the absence of disease progression or unacceptable toxicity.

T-CELL INFUSION: Patients receive autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells IV over 15-30 minutes on day 0.

After completion of study treatment, patients are followed up within 3 days after T-cell infusion and at 1, 2, 3, 4, 6, and 8 weeks, then at 3, 6, and 12 months, then periodically for up to 15 years. ;

Related Conditions & MeSH terms

• B Acute Lymphoblastic Leukemia With t(v;11q23.3); KMT2A Rearranged
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent B Acute Lymphoblastic Leukemia
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Recurrent Mantle Cell Lymphoma
• Recurrent Non-Hodgkin Lymphoma
• Recurrent Ph-Like Acute Lymphoblastic Leukemia
• Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
• Recurrent Small Lymphocytic Lymphoma
• Refractory B Acute Lymphoblastic Leukemia
• Refractory Chronic Lymphocytic Leukemia
• Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Refractory Mantle Cell Lymphoma
• Refractory Non-Hodgkin Lymphoma
• Refractory Ph-Like Acute Lymphoblastic Leukemia
• Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma
• Refractory Small Lymphocytic Lymphoma

• NCT number: NCT03579888
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: June 26, 2020
• Completion date: May 27, 2021