A Phase 1/2 Safety, Dose-finding, and Pharmacokinetics Study of VNX-101 Gene Therapy in Patients With Relapsed or Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia

Description

This is a Phase 1/2, first-in-human, open-label, dose-escalating trial designed to assess the safety and efficacy of VNX-101 in patients with relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia (ALL).VNX-101 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-CD19/anti-CD3 scFv diabody (termed GP101). GP101 binds both cluster of differentiation (CD)19 and CD3, inducing T-cells to kill both benign and malignant B-cells. Following a single intravenous (IV) infusion, the vector induces the liver and key tissues to continuously secrete GP101 into the bloodstream, resulting in long-term, consistent serum levels of GP101. Potential advantages of VNX-101 over autologous CAR-T therapy include it is off-the-shelf, provides a gentle onset of action, does not require lymphodepletion chemotherapy, engages all T-cells continuously (including those freshly produced from the bone marrow), and utilizes highly efficient signaling through the

Trial Eligibility

Inclusion Criteria: * Age: Part 1: 18-90 years of age, Part 2: 13-90 years of age * Relapsed B-cell ALL with bone marrow blasts \>= 5% * Refractory B-cell ALL as defined in the protocol * Bone marrow blasts requirement (flow cytometry): Part 1: \>0.01% to \<5% prior to VNX-101 dosing, Part 2: \>0.01% to \<50% prior to VNX-101 dosing. * Ineligible or declined CAR-T therapy or failed to respond or relapsed after such therapy * If prior blinatumomab treatment, cells remain CD19+ and not refractory to blinatumomab * AAVrh74 total antibody \<1:400 * Protocol-specified ranges for renal, liver, cardiac and pulmonary function * Protocol-specified ranges for hematology parameters Exclusion Criteria: * Hepatoxicity (AST or ALT \> 2x upper limit of normal) * History of thrombotic microangiopathy or cardiomyopathy, or evidence of sensory neuropathy * Pregnant or nursing (lactating) women * Acute Graft versus Host Disease (GvHD): Grade 2-4 or chronic GvHD of any grade * History of hypersensitivity to corticosteroids or history of corticosteroid-related toxicity * Chemotherapy given within the protocol-specified discontinuation timelines Other Inclusion/Exclusion criteria to be applied per protocol.

Study Info

Interventions

Locations Recruiting

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