Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title: A Phase I Trial of CD19-Targeted Chimeric Antigen Receptor (CAR) Modified T Cells Genetically Engineered to Secrete Interleukin 12 (IL-12) and With a Truncated Human Epidermal Growth Factor Receptor (EGFRt) in Patients With Relapsed or Refractory CD19+ Hematologic Malignancies

Status Recruiting

Clinical Trial Summary

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells called EGFRt/19-28z/IL-12 CAR T cells, and to see how they work in treating patients with hematologic malignancies that makes a protein called CD19 (CD19-positive) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Chimeric Antigen Receptor (CAR) T-cell Therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. To improve the effectiveness of the modified T cells and to help the immune system fight cancer cells better, the modified T cells given in this study will include a gene that makes the T cells produce a cytokine (a molecule involved in signaling within the immune system) called interleukin-12 (IL-12). The researchers think that IL-12 may improve the effectiveness of the modified T cells, and it may also strengthen the immune system to fight cancer. Giving EGFRt/19-28z/IL-12 CAR T cells may be safe and tolerable in treating patients with relapsed or refractory CD19+ hematologic malignancies.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety, toxicity and maximum tolerated dose (MTD) of EGFRt/19-28z/IL-12 CAR T-lymphocytes (EGFRt/19-28z/IL-12 CAR T cells) in patients with relapsed or refractory CD19+ aggressive hematologic malignancies.

SECONDARY OBJECTIVES:

I. To assess the anti-tumor efficacy of adoptively transferred EGFRt/19-28z/IL-12 T cells.

II. To assess the in vivo persistence of adoptively transferred EGFRt/19-28z/IL-12 T cells.

EXPLORATORY OBJECTIVES:

I. To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

II. To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

III. To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.

IV. To determine the proportion of evaluable patients who achieve minimal residual disease (MRD)-negativity in peripheral blood and/or bone marrow.

V. To assess phenotype and in vitro function of end-of-production (EOP) EGFRt/19-28z/IL-12 CAR T cells and phenotype at recovery following CAR T cell administration.

OUTLINE: This is a dose-escalation study of EGFRt/19- 28z/IL-12 CAR T cells. Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells intravenously (IV) over 5 to 30 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET) as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

COHORT B: Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

After completion of study treatment, patients are followed up weekly for 4 weeks, every 4 weeks until 24 months, every 3 months thereafter for 1 year, then annually for up to 5 years, followed by long-term follow up for up to 15 years. ;

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Recurrence
• Recurrent Chronic Lymphocytic Leukemia
• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Follicular Lymphoma
• Recurrent High Grade B-Cell Lymphoma
• Recurrent Mantle Cell Lymphoma
• Recurrent Transformed Chronic Lymphocytic Leukemia
• Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Follicular Lymphoma
• Refractory High Grade B-Cell Lymphoma
• Refractory Mantle Cell Lymphoma
• Refractory Transformed Chronic Lymphocytic Leukemia
• Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

• NCT number: NCT06343376
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Recruiting
• Phase: Phase 1
• Start date: June 15, 2024
• Completion date: June 15, 2029