NCT02159495

Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

Phase I Study of Cellular Immunotherapy Using T Cells Lentivirally Transduced to Express a CD123-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Antigen Receptor and a Truncated EGFR for Patients With CD123+ Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of genetically modified T-cells after lymphodepleting chemotherapy in treating patients with acute myeloid leukemia or blastic plasmacytoid dendritic cell neoplasm that has returned after a period of improvement or has not responded to previous treatment. An immune cell is a type of blood cell that can recognize and kill abnormal cells in the body. The immune cell product will be made from patient or patient's donor (related or unrelated) blood cells. The immune cells are changed by inserting additional pieces of deoxyribonucleic acid (DNA) (genetic material) into the cell to make it recognize and kill cancer cells. 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 anti-tumor activity and safety of administering ex vivo expanded T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a co-stimulatory CD123-specific chimeric antigen receptor (CAR) as well as a truncated EGFR (CD123CAR-CD28-CD3zeta-EGFRt+ T cells \[CD123+ CAR T cells\]) following lymphodepletion for patients with CD123+ relapsed or refractory acute myeloid leukemia (AML) (arm 1), or CD123+ persistent or recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) (arm 2). II. To determine the recommended Phase II dose (RP2D) for both arms (AML and BPDCN). SECONDARY OBJECTIVES: I. To assess activity in the form of CD123+ CAR T cell persistence, 6 month progression free survival (PFS 6mo) rate, and 1 year overall survival (OS) rate, and describe the immunogenicity of CD123R(EQ)28zeta/EGFRt+ T cells. TERTIARY OBJECTIVES: I. To assess impact on hematopoiesis, change from baseline in numbers of CD123+ blood cells, CD123 expression on malignant cells and hematopoietic cells, and the clinical efficacy of EGFRt mediated CAR T cell ablation. OUTLINE: This is a dose-escalation study of autologous or allogeneic (related or unrelated donor) CD123+ CAR T cells. Patients undergo a lymphodepleting regimen 3-10 days prior to CD123+ CAR T cell infusion as determined by the principal investigator and the protocol team. Patients receive either cyclophosphamide intravenously (IV) on days -4 and/or -3; fludarabine phosphate and cyclophosphamide IV on days -5 to -3; fludarabine phosphate IV on days -5 to -3 and cyclophosphamide IV on days -4 and/or -3. Patients receive autologous or allogeneic CD123+ CAR T cells IV over 15 minutes on day 0. Patients with evidence of disease at \> 28 days, continuing expression of the CD123 antigen, and not having experienced a dose-limiting toxicity (DLT) may receive a second infusion of CD123+ CAR T cells after 28 days. After completion of study treatment, patients are followed up at 24 hours, then every 2 days for up to 14 days, every week for 1 month, every month for 1 year and then yearly for 15 years.

Conditions

• Adult Acute Myeloid Leukemia in Remission
• Acute Biphenotypic Leukemia
• Early Relapse of Acute Myeloid Leukemia
• Late Relapse of Acute Myeloid Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Acute Myeloid Leukemia
• Adult Acute Lymphoblastic Leukemia
• Interleukin-3 Receptor Subunit Alpha Positive
• Minimal Residual Disease
• Refractory Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	cyclophosphamide	Given IV
BIOLOGICAL	Autologous CD123CAR-CD28-CD3zeta-EGFRt-expressing T Lymphocytes	Given IV
OTHER	laboratory biomarker analysis	Correlative studies
BIOLOGICAL	Allogeneic CD123CAR-CD28-CD3zeta-EGFRt-expressing T-lymphocytes	Given IV
DRUG	Fludarabine Phosphate	Given IV

Timeline

• Start date: 2015-12-15
• Primary completion: 2026-08-06
• Completion: 2026-08-06
• First posted: 2014-06-10
• Last updated: 2025-09-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study