Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Anti-CD7 Allogeneic CAR T-Cells (WU-CART-007) in Patients With CD7+ Hematologic Malignancies

Summary

Effective treatment options for relapsed/refractory acute myeloid leukemia (AML) and T-cell non-Hodgkin lymphoma (T-NHL) represent a significant unmet medical need. CAR T therapy has offered durable remissions and potential cures in some forms of hematologic malignancy, including B-cell acute lymphoblastic leukemia. In AML, however, CAR T approaches have been limited by the lack of suitable antigens, as most myeloid markers are shared with normal hematopoietic stem cells and targeting of these antigens by CAR T therapy leads to undesirable hematologic toxicity. Similarly, T-NHL has not yet benefited from CAR T therapy due to a lack of suitable markers. One potential therapeutic target is CD7, which is expressed normally on mature T-cells and NK-cells but is also aberrantly expressed on \~30% of acute myeloid leukemias. CAR T therapy for patients with CD7+ AML and T-NHL will potentially offer a new therapeutic option which has a chance of offering durable benefit.

WU-CART-007 is a CD7-directed, genetically modified, allogeneic, fratricide-resistant chimeric antigen receptor (CAR) T-cell product for the treatment of CD7+ hematologic malignancies. These cells have two key changes from conventional, autologous CAR T-cells. First, because CD7 is present on normal T-cells including conventional CAR T products, CD7 is deleted from WU CART-007. This allows for targeting of CD7 without the risk of fratricide (killing of WU-CART-007 cells by other WU-CART-007 cells). Second, the T cell receptor alpha constant (TRAC) is also deleted. This makes WU CART 007 cells incapable of recognizing antigens other than CD7 and allows for the use of an allogeneic product without causing Graft-versus-Host-Disease (GvHD).

Conditions

• T-Cell Non-Hodgkin Lymphoma
• Acute Myeloid Leukemia
• Angioimmunoblastic T-cell Lymphoma
• Enteropathy-Associated T-Cell Lymphoma
• Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
• Peripheral T Cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Adult T Cell Leukemia
• Adult T Cell Lymphoma
• T Cell Prolymphocytic Leukemia
• Extranodal NK/T-cell Lymphoma
• Transformed Mycosis Fungoides
• Sezary Syndrome
• Primary Cutaneous Gamma-Delta T-Cell Lymphoma
• Hepatosplenic T-cell Lymphoma

Interventions

BIOLOGICAL

WU-CART-007

Provided by Miltenyi Biotec

Sponsors & Collaborators

• Wugen, Inc.

  collaborator INDUSTRY

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Geoffrey Uy, M.D. · Washington University School of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-10-10

Primary Completion

2026-06-30

Completion

2026-06-30

FDA Drug

Yes

Countries

• United States

Study Locations