Off-the-shelf CAR-T Allo-QuadCAR01-T targeting CD19 and CD20 for relapsed or refractory B‑cell cancers

A Single-arm, Multicenter, Open-label, Phase I/II Trial of Allo-QuadCAR01-T, an Allogeneic CAR-T-cell Therapy Targeting CD19 and CD20, for the Treatment of Relapsed or Refractory B-cell Malignancies

This study will test an off-the-shelf donor CAR-T that targets CD19 and CD20 to try to treat adults with relapsed or refractory B‑cell lymphomas or leukemias.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 178 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AvenCell Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: CAR-T, radiation, chemotherapy
• Locations: 13 sites (Chicago, Illinois and 12 other locations)
• Trial ID: NCT07284433 on ClinicalTrials.gov

What this trial studies

Allo-QuadCAR01-T is a gene-edited, donor-derived CAR-T product designed to target both CD19 and CD20 to reduce relapse risk and improve safety. The trial has three parts: dose escalation to find a safe dose, dose confirmation, and a phase focused on efficacy in diffuse large B-cell lymphoma. Participants receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) followed by a single infusion of the allogeneic CAR-T product and are monitored for safety and tumor response. About 160 adults will be enrolled with follow-up visits extending up to 15 years for long-term outcomes.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory B‑cell non-Hodgkin lymphoma or chronic lymphocytic leukemia who have had at least two prior therapies, ECOG 0–1, adequate organ function, an HLA B/C match with donor cells, and no active uncontrolled infections.

Not a fit: Patients with a recent CAR-T (within 3 months), prior allogeneic transplant, active CNS involvement (in early cohorts), history of graft-versus-host disease, certain autoimmune autoantibodies, or uncontrolled infections are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, this could provide a ready-made CAR-T option that reaches patients faster, may lower costs, and could reduce relapse by targeting two antigens.

How similar studies have performed: Early trials of allogeneic CD19 CAR-T products have shown encouraging responses, but gene-edited, dual CD19/CD20 donor CAR-T products like Allo-QuadCAR01-T are relatively novel and not yet proven in large studies.

Eligibility criteria

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.

Where this trial is running

Chicago, Illinois and 12 other locations

• University of Chicago — Chicago, Illinois, United States (Not_yet_recruiting)
• Northwestern University — Evanston, Illinois, United States (Not_yet_recruiting)
• Brown University Health — Providence, Rhode Island, United States (Not_yet_recruiting)
• Sarah Cannon Research Institute — Nashville, Tennessee, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Not_yet_recruiting)
• Universitätsklinikum Ulm — Ulm, Baden-Wurttemberg, Germany (Recruiting)
• Universitätsklinikum Erlangen — Erlangen, Bavaria, Germany (Recruiting)
• Klinikum der Universität München — Munich, Bavaria, Germany (Not_yet_recruiting)
• Universitätsklinikum Marburg — Marburg, Hesse, Germany (Not_yet_recruiting)
• Uniklinikum Erlangen — Essen, North Rhine-Westphalia, Germany (Not_yet_recruiting)
• Universitätsklinikum Dresden — Dresden, Saxony, Germany (Recruiting)
• Charité Universitätsmedizin Berlin — Berlin, Germany (Recruiting)
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (Not_yet_recruiting)

Study contacts

• Study coordinator: Antje Warth, Dr.

Conditions Lymphoma Diffuse Large B-cell; Leukemia and Lymphoma; Leukemia Relapse; Lymphoma Receiving CAR-T Therapy