Humanized CD19-Specific CAR T Cells for the Treatment of Patients With Positive Relapsed or Refractory CD19 Positive B-Cell Acute Lymphoblastic Leukemia

Refractory Acute Lymphoblastic Leukemia Clinical Trial

Official title: Phase Ib Study to Evaluate Humanized CD19-Specific CAR T Cells Following Lymphodepleting Chemotherapy in Adult Patients With Relapsed/Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia

Status Recruiting

Clinical Trial Summary

This phase Ib trial tests the safety, side effects, and effectiveness of humanized (hu)CD19-chimeric antigen receptor (CAR) T cell therapy in treating patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy is a 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, such as CD19, 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 huCD19 positive CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. huCD19-CAR T cell therapy may be safe, tolerable and effective in treating patients with relapsed or refractory CD19 positive ALL.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Assess the safety and tolerability of Tn/mem-enriched huCD19(VH4VK1)(dCH2)BBzeta/EGFRt+ T cells (huCD19 CAR T) as single-dose monotherapy by evaluation of toxicities including type, frequency, severity, attribution, time course and duration.

II. Determine the maximum feasible dose (MFD)/recommended phase 2 dose(s) schedule (RP2D) of huCD19 CAR T as single-dose monotherapy on relapsed/refractory (r/r) ALL patients.

SECONDARY OBJECTIVES:

I. Obtain preliminary estimates of complete remission (complete remission [CR] /complete response with incomplete bone marrow recovery [CRi]) rate(s).

II. Overall response rate (CR, CRi): best response. III. Duration of response (CR, CRi). IV. Minimal residual disease (MRD)- negative CR/CRi. V. The number and rate of bridging to transplant. VI. Estimate the progression free survival (PFS) and overall survival (OS) rate, at 6-months and 1-year post (first) huCD19 CAR T cell infusion.

EXPLORATORY OBJECTIVES:

I. Access the expansion and persistence of T cell via flow cytometry in blood, bone marrow (BM) and cerebrospinal fluid (CSF).

II. Assess the phenotype and activation status of CAR T via flow cytometry, polymerase chain reaction (PCR), and cytokine analysis.

III. Assess CAR T cell clonal expansion and repertoires of endogenous T cells. IV. Assess immunophenotyping and functional analyses of CAR T cell products. V. Determine the role of the immunologic milieu. VI. Evaluation of B cell aplasia. VII. Serum cytokine measurement. VIII. Tumor antigen analysis. XIV. Evaluation of Immunogenicity by enzyme-linked immunosorbent assay (ELISA). X. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred huCD19-CAR T cells.

OUTLINE: This is a dose-escalation study of huCD19-CAR T, followed by a dose-expansion study.

Patients undergo leukapheresis then receive lymphodepletion chemotherapy with fludarabine ntravenously (IV) and cyclophosphamide IV on days -5, -4 and -3 and huCD19-CAR T IV cells over 10-15 minutes on day 0. Patients may optionally receive cetuximab IV over 60-120 minutes at least 28 days post T cell infusion and undergo allogeneic hematopoietic cell transplantation (alloHCT). Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan ((MUGA), computed tomography (CT) or positron emission tomography (PET)/CT and optional magnetic resonance imaging (MRI) on study and bone marrow biopsy and aspiration and blood sample collection throughout the study.

After completion of study treatment, patients are followed up monthly for 1 year then yearly for up to 15 years. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia

• NCT number: NCT06447987
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Recruiting
• Phase: Phase 1
• Start date: August 6, 2024
• Completion date: August 6, 2025