Leukemia and Lymphoma, Leukemia Relapse, Lymphoma Diffuse Large B-cell, Lymphoma Receiving CAR-T Therapy
Conditions
Brief summary
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.
Interventions
Intravenous infusion over 3 days (d-5 to d-3)
Intravenous infusion over 3 days (d-5 to d-3)
DRUGAllo-QuadCAR01-T
Single dose IV infusion on Day 1
Sponsors
AvenCell Therapeutics, Inc.
AvenCell Europe GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AEs defined as DLTs | At the end of cycle 1 (in total 28 days, given no treatment interruptions) | Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria |
| To determine the maximum tolerated dose (MTD) | At the End of Cycle 1 (in total 28 days, given no treatment interruptions) | MTD |
| To determine the incidence of dose-limiting toxicities (DLT) | At the end of cycle 1 (in total 28 days, given no treatment interruptions) | Incidence of DLTs |
| Phase 2: Complete response rate (CRR) | Up to week 13 | Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Allo-QuadCAR01-T in PB in patients after infusion of Allo-QuadCAR01-T | Up to 24 months | Detection of VCN in blood samples |
| To investigate the impact of Allo-QuadCAR01-T on MRD | Up to 24 months | MRD levels in responding CLL patients |
| To evaluate immunogenicity against Allo-QuadCAR01-T | Up to 24 months | Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T |
| To evaluate host immune cell depletion and reconstitution resulting from LD | Up to 24 months | Enumeration of host PB B-cell, T cell, and NK cell numbers |
| Overall Response Rate (ORR) | Up to 24 months | ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma, anti-CLL therapy or local radiotherapy for lymphoma , per the Lugano Classification, as determined by the investigator. |
| Progression-Free Survival (PFS) | Up to 24 months | PFS is defined as the time from Allo-QuadCAR01-T infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause. |
| Duration of Response (DOR) | Up to 24 months | DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator. |
| Overall Survival (OS) | Up to 24 months | OS is defined as the time from Allo-QuadCAR01-T infusion to death from any cause. |
| Time to Next Treatment (TTNT) | Up to 24 months | TTNT is defined as time from Allo-QuadCAR01-T infusion to the start of subsequent new anti-lymphoma, anti-CLL therapy or local radiotherapy for lymphoma. |
Countries
Germany, United States
Contacts
CONTACTAntje Warth, Dr.
CONTACTKatja Jersemann, Dr.
Outcome results
None listed