NCT04097301

Study of CAR T-cell Therapy in Acute Myeloid Leukemia and Multiple Myeloma

A Phase I-IIa Trial to Assess the Safety and Antitumor Activity of Autologous CD44v6 CAR T-cells in Acute Myeloid Leukemia and Multiple Myeloma Expressing CD44v6

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: AGC Biologics S.p.A. · Industry
• Sex: All
• Age: 1 Year – 75 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this first-in-man Phase I-IIa study is to evaluate the safety and antitumor activity of autologous CD44v6 CAR T-cells in patients with acute myeloid leukemia (AML) and multiple myeloma (MM).

Detailed description

The study is a seamless Phase I/IIa, open-label, multicenter clinical trial that combines Phase I dose escalation based on toxicity with Phase IIa dose expansion based on antitumor activity. Considering the "first in human" nature of this clinical study, the Bayesian Optimal Interval Design (BOIN) has been chosen to minimize any risks of exposure to the novel CD44v6 CAR T-cells during dose escalation. The study population is made up of patients with relapsed/refractory AML or MM expressing CD44v6. The medicinal product under investigation (MLM-CAR44.1 T-cells) is patient specific as it is prepared starting from lymphocytes of the patient collected through lymphocyte apheresis. These autologous T-cells are expanded in vitro in large numbers and genetically modified to express the CAR CD44v6ΔNL gene and thus acquire antitumor functions. As a safety feature, the MLM-CAR44.1 T-cells are genetically modified to also express the HSV-TK Mut2 gene (suicide gene), which can be selectively activated in case of severe toxicity through the administration of ganciclovir (GCV), leading to the death of proliferating CAR T-cells. The aim of this study is to assess the safety, antitumor activity and feasibility of CD44v6 CAR T cell immunotherapy in AML and MM.

Conditions

• Acute Myeloid Leukemia
• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	MLM-CAR44.1 T-cells at day 0 Single intravenous infusion	Lymphodepleting chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) daily from day -5 to day -3.

Timeline

• Start date: 2019-08-27
• Primary completion: 2021-06-18
• Completion: 2021-06-18
• First posted: 2019-09-20
• Last updated: 2022-01-19
• Results posted: 2022-01-19

Locations

3 sites across 2 countries: Czechia, Italy