NCT02146924

Cellular Immunotherapy in Treating Patients With High-Risk Acute Lymphoblastic Leukemia

Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With High-Risk CD19+ Acute Lymphoblastic Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of cellular immunotherapy in treating patients with high-risk acute lymphoblastic leukemia. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To examine the activity and safety of adoptive therapy using ex vivo expanded memory T cells that are enriched and genetically-modified to express a CD19-specific, hinge optimized, CD28-costimulatory chimeric antigen receptor (CAR) as well as a truncated human EGFR (Arm 1: CD19R(EQ)28zeta/truncated human EGFR \[EGFRt\]+ central memory T cells \[TCM\]; Arm 2: CD19R(EQ)28zeta/EGFRt+ naive and memory T cells \[TN/NEM\]) shortly following a lymphodepleting preparative regimen for adults with poor prognosis CD19+ acute lymphoblastic leukemia (ALL). II. To determine the Phase II recommended dose (RP2D). III. To expand the maximum tolerated dose (MTD) dose to better describe the activity and safety of this dose. SECONDARY OBJECTIVE: I. To study additional antitumor activity endpoints of CD19R(EQ)28zeta/EGFRt+ TCM and CD19R(EQ)28zeta/EGFRt+ TN/NEM. OUTLINE: This is a dose-escalation study. ARM I (CLOSED TO ACCRUAL JANUARY 2019): Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells after 28 days. ARM II: Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells after 28 days. After completion of study treatment, patients are followed up at 24 hours, weekly for 1 month, monthly for 1 year, and then yearly for at least 15 years.

Conditions

• B Acute Lymphoblastic Leukemia
• Recurrent Acute Lymphoblastic Leukemia
• Refractory Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes	Given IV
BIOLOGICAL	CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2014-10-16
• Primary completion: 2026-07-15
• Completion: 2026-07-15
• First posted: 2014-05-26
• Last updated: 2025-12-05

Locations

1 site across 1 country: United States