Study of Allo-QuadCAR01-T, an Allogeneic CAR-T Targeting CD19/CD20, in Patients With Relapsed or Refractory B-Cell Malignancies
Purpose
This study is testing Allo-QuadCAR01-T, a new off-the-shelf CAR-T therapy for people with hard-to-treat B-cell cancers. Unlike current CAR-T treatments that use a patient's own cells, this therapy uses donor cells that are ready to use, which can save time and reduce costs. It targets two proteins, CD19 and CD20, to lower the chance of relapse and uses gene editing to make it safer. The trial has three parts: first to find a safe dose, then to confirm it, and finally to test how well it works in patients with diffuse large B-cell lymphoma (DLBCL). Patients will get one infusion after chemotherapy to prepare their body. The main goal is to check safety and see how many patients have a complete response by Week 13. About 160 patients will take part, and researchers will follow them for up to 15 years.
Conditions
- Lymphoma Diffuse Large B-cell
- Leukemia and Lymphoma
- Leukemia Relapse
- Lymphoma Receiving CAR-T Therapy
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adults 18 years or older. - Diagnosed with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL). - Must have received at least 2 prior lines of therapy. - ECOG performance status 0-1 (able to carry out daily activities). - Adequate organ function (heart, liver, kidneys). - HLA B/C match with donor cells. - No active uncontrolled infections.
Exclusion Criteria
- Active CNS involvement (including PCNSL) in dose escalation cohorts; may be allowed in later cohorts with Sponsor approval. - Prior CAR-T within 3 months of screening, or ≥Grade 3 ICAHT from prior CAR-T. - Autologous stem cell transplant within 3 months. - Prior allogeneic stem cell transplant or solid organ transplant. - Prior therapy with dual CD19/CD20 CAR-T. - Severe hypersensitivity to trial agents or similar compounds. - History of GvHD or post-transplant lymphoproliferative disorder. - Presence of La/SS-B autoantibodies or related autoimmune diseases. - Other malignancy that may interfere with trial, except: - Curatively treated basal/squamous skin cancer or cervical carcinoma in situ - Low-grade, early-stage prostate cancer (Gleason ≤6, Stage 1-2) with no therapy needed - Adjuvant endocrine therapy for non-metastatic breast cancer (≥2 years) - Any other curatively treated malignancy in remission ≥2 years - Active viral infection within 1 week of screening, or serious bacterial/fungal infection. - Hemorrhagic cystitis. - Active neuro-autoimmune disease (e.g., MS, Guillain-Barré, ALS). - Active or residual HBV, HCV, or syphilis. - Active HIV. History of HIV may be eligible with Sponsor approval if: - Neurological disorders within 6 months (e.g., stroke, dementia, Parkinson's, cerebellar disease, CNS autoimmune disease). - Significant cardiac disease within 6 months (e.g., MI, stent, unstable angina). - Primary immunodeficiency or autoimmune disease requiring systemic treatment within 1 year (unless stable and Sponsor-approved). - Unresolved ≥Grade 2 non-hematologic toxicity from prior therapy (except neuropathy up to Grade 2). - Systemic immunosuppression within 28 days. - Last systemic lymphoma/CLL therapy (standard or investigational) within 28 days or 5 half-lives. - Major surgery within 14 days. - Local radiation within 28 days. - Live vaccination within 28 days. - Pregnant or breastfeeding.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- The trial is structured in three parts: Phase Ia uses a dose-escalation approach to find a safe starting dose of Allo-QuadCAR01-T. Phase Ib expands testing at the selected dose in patients with diffuse large B-cell lymphoma (DLBCL) and possibly other subtypes to confirm safety and early effectiveness. Phase II focuses on a larger group of DLBCL patients to measure how well the treatment works at the recommended dose. All participants receive a single infusion of the therapy after a short course of chemotherapy to prepare their immune system. Patients are closely monitored for 13 weeks, then every three months for two years, with an additional long-term follow-up lasting up to 15 years.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Allo-QuadCAR01-T |
Phase Ia (Escalation): Participants with relapsed or refractory B-cell malignancies will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T. Phase Ib (Expansion): After dose escalation, additional participants with relapsed or refractory B-cell lymphoma will receive lymphodepleting chemotherapy followed by a single infusion of Allo-QuadCAR01-T at one or more tolerable dose levels from Phase Ia. Phase II: Participants with relapsed or refractory DLBCL will receive lymphodepleting chemotherapy, followed by a single infusion of Allo-QuadCAR01-T at the recommended Phase II dose. The primary endpoint is complete response rate at Week 13, with secondary endpoints including duration of response, progression-free survival, and overall survival. |
|
Recruiting Locations
Sarah Cannon Research Institute
Nashville, Tennessee 37203
Nashville, Tennessee 37203
More Details
- Status
- Recruiting
- Sponsor
- AvenCell Therapeutics, Inc.