Gene Therapy for B-Cell Acute Lymphoblastic Leukemia

Trial Title: Gene Therapy for B-Cell Acute Lymphoblastic Leukemia

NCT ID: NCT06533579

Condition: B-cell Acute Lymphoblastic Leukemia

Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Genetic
Intervention name: Dose Level 1, VNX-101
Description: Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Arm group label: Group 1/Group 2/Group 3/Group 4

Intervention type: Genetic
Intervention name: Dose Level 2, VNX-101
Description: Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Arm group label: Group 1/Group 2/Group 3/Group 4

Intervention type: Genetic
Intervention name: Dose Level 3, VNX-101
Description: Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Arm group label: Group 1/Group 2/Group 3/Group 4

Intervention type: Genetic
Intervention name: Dose Level 4, VNX-101
Description: Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Arm group label: Group 1/Group 2/Group 3/Group 4

Summary: 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).

Detailed description: 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 native T-cell receptor. In this 2-part study, dose-finding data from Part 1 of the study (n=~12 patients with marrow blasts <5%) will be used determine the dose for Part 2 in patients at higher disease burden (marrow blasts <50%). Part 1 is a dose-finding PK study in adults ≥18 years old designed to determine the minimal dose that achieves target PK serum levels of GP101 at steady state (8-week timepoint) without dose-limited toxicities, defined as the recommended Part 2 dose (RP2D). Prior to VNX-101 dosing, subjects may undergo standard of care chemotherapy to meet dosing criteria. Part 2 (n=~14) will be opened following data safety monitoring board review of Part 1 data and is designed to determine the safety and pharmacokinetics (PK) of VNX-101 at the RP2D in a broader array of subjects with higher leukemic burden (i.e. bone marrow blasts <50%). The age range for Part 2 will be expanded to include subjects ≥13 years old. Patients will be followed for safety and efficacy up to 5 years post VNX-101 dosing. Long-term follow-up assessments for safety will be conducted for 6 to 15 years post VNX-101 dosing.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 13 Years

Maximum age: 90 Years

Healthy volunteers: No

Locations:

Facility:
Name: Colorado Blood Cancer Institute

Address:
City: Denver
Zip: 80218
Country: United States

Status: Recruiting

Contact:
Last name: Clinical Trial Information Line

Phone: 720-754-4835

Facility:
Name: Oncology Hematology Care

Address:
City: Cincinnati
Zip: 45242
Country: United States

Status: Recruiting

Contact:
Last name: Clinical Trial Information Line

Phone: 888-649-4800

Facility:
Name: TriStar BMT

Address:
City: Nashville
Zip: 37203
Country: United States

Status: Recruiting

Contact:
Last name: Stephen Strickland, MD

Phone: 615-329-7274
Email: stephen.strickland@hcahealthcare.com

Start date: November 15, 2024

Completion date: September 2031

Lead sponsor:
Agency: Vironexis Biotherapeutics Inc.
Agency class: Industry

Source: Vironexis Biotherapeutics Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06533579