Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Dose Level 1, VNX-101, Dose Level 2, VNX-101, Dose Level 3, VNX-101, Dose Level 4, VNX-101.
- Who it may be relevant to
- Registry conditions: B-cell Acute Lymphoblastic Leukemia, Large B-cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma. Basic parameters: 13 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 1/2 Safety, Dose-finding, and Pharmacokinetics Study of VNX-101 Gene Therapy in Patients With Relapsed or Refractory CD19-Positive Hematologic Malignancies (SENTRY-CD19)
Overview
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-positive hematologic malignancies.
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) will be used determine the dose for Part 2 in patients. 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=\~20) 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. 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.
Interventions
- Genetic Dose Level 1, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion - Genetic Dose Level 2, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion - Genetic Dose Level 3, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion - Genetic Dose Level 4, VNX-101
Adeno-associated viral vector encoding the CD3/CD19 Bi-Specific T-Cell Engager (AAV.CD3/CD19), Single IV infusion
Primary outcome measures
- Treatment emergent adverse events (TEAEs) and treatment-emergent serious events (TESAEs) [Time frame: Change from Baseline to Year 5 post dosing]
Secondary outcome measures (4)
- Change from baseline in B-cell counts [Time frame: Change from baseline to year 5 post dosing]
- Change baseline in immunoglobulin levels [Time frame: Change from baseline to year 5 post dosing]
- Change baseline in antitumor activity [Time frame: Change from baseline to year 5 post dosing]
- Proportion/duration of subjects achieving response, progression free survival, and disease free survival. [Time frame: Change from baseline to year 5 post dosing]
Eligibility criteria
Inclusion criteria
- Age: Part 1: 18-90 years of age, Part 2: 13-90 years of age
- Relapsed or refractory CD-19 positive leukemia or lymphoma as defined in the protocol
- CD19-positive expression
- AAV specified capsid 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 11 centers
- City of Hope — Duarte
- Valkyrie Clinical Trials — Los Angeles
- Colorado Blood Cancer Institute — Denver
- Mayo Clinic, Clinical Trials Referral Office — Jacksonville
- Mayo Clinic, Clinical Trials Referral Office — Rochester
- New York Medical College — Valhalla
- University of North Carolina at Chapel Hill/ University of North Carolina Medical Center — Chapel Hill
- The Ohio State University Wexner Medical Center — Columbus
- … and 3 more centers
Identifiers
NCT: NCT06533579 · VNX-101-01