ALLO-QUADCAR01-T for Relapsed or refractory B-cell non-Hodgkin lymphoma | Chronic lymphocytic leukaemia

Inclusion criteria

• {"criterion_text":"- 1. Male or female, ≥ 18 years old.\n- 2. Willing and able to give written informed consent.\n- 3. Have histologically confirmed R/R B-NHL or CLL, per WHO classification, expected to express CD19 and/or CD20, have received, deemed ineligible for, or have declined standard therapies reimbursed by their health care system, have received a minimum of 2 treatment lines, and have a clinical need for systemic treatment. • Large B-cell lymphoma (LBCL) (including e.g., diffuse large B-cell lymphoma (DLBCL), High-grade BCL (HGBL), transformed LBCL from indolent lymphoma or CLL, Primary mediastinal large B-cell lymphoma (PMBCL) – but not primary CNS lymphoma (PCNSL)) • Follicular lymphoma (FL) • Marginal zone lymphoma (MZL) • Mantle cell lymphoma (MCL) • Chronic lymphocytic leukemia/Small lymphocytic leukemia (CLL/SLL)\n- 4. For lymphomas (including SLL), measurable disease with at least 1 bi-dimensional measurable lesion (CT/MRI), longest diameter > 1.5 cm for nodal, > 1 cm for extra-nodal within a month of the treatment start, and after any anti-lymphoma therapies. Previously radiated lesions are eligible only if there is documented progression on the site after radiation therapy. Only MRD positivity is not considered eligible.\n- 5. For CLL, indication for treatment per iwCLL 2018 guideline and objectively measurable disease (e.g., lymphocytosis or measurable lesion, including lymphadenopathy, splenomegaly, and extra-nodal lesions, but not e.g., autoimmune manifestations only, or MRD positivity).\n- 6. Fresh or archival biopsy sample available (obtained after last systemic treatment line), or willingness to provide one for retrospective CD19/CD20 expression analysis. A patient may be included without biopsy material with Sponsor approval if the biopsy procedure would cause unacceptable safety risk or discomfort.\n- 7. HLA B and C types match 1 or more of the available IMP batches.\n- 8. ECOG 0 to 1.\n- 9. Adequate organ function: • Calculated CrCl ≥ 60 mL/min Note: CrCl must be calculated using the Cockcroft-Gault Method: CrCl = ((140 – age) × weight)/(72 × SCr)) [× 0.85 (if female)] CrCl = mL/minute; Age = years; Weight = kg; SCr = mg/dL • Direct bilirubin ≤ 1.5 × ULN (unless Gilbert’s syndrome) • AST/ALT ≤ 2.5 × ULN (up to 5 × ULN if elevation directly caused by lymphoma infiltration) • LVEF ≥ 45% (per local standard method, e.g., transthoracic echocardiography) • Oxygen saturation ≥ 92% on room air • Blood counts: - ANC ≥ 1.0 × 10^9 L (≥ 0.75 × 10^9 /L may be eligible with Sponsor approval) - Platelets ≥ 50 × 10^9 /L - Hb ≥ 7 g/dL Note: Lower levels may be allowed after Sponsor approval if cytopenia directly caused by lymphoma/CLL infiltration.\n- 10. Life expectancy of ≥ 3 months as assessed by the Investigator.\n- 11. Central venous access or willingness to have one.\n- 12. Weight is greater than the minimum weight required for a specific batch to ensure that the dose administered does not exceed 10^5 TCR+ cells/kg of patient weight.\n- 13. A woman of childbearing potential (WOCBP) may be enrolled if she has a negative serum pregnancy test at Screening visit and is willing to use a highly effective method of birth control (Pearl index of ≤ 1 required) resulting in a low failure rate (e.g., hormonal contraception, intrauterine device, total sexual abstinence, or sterilization) for at least 12 months after LD chemotherapy. Male patients must also practice a highly effective method of birth control and should not father a child or donate sperm for at least 6 months after end of LD chemotherapy."}

Exclusion criteria

• {"criterion_text":"- 1. Active CNS involvement (including PCNSL) is excluded from dose escalation cohorts. However, these individuals may be enrolled to established safe dose cohorts (i.e., backfill cohorts, dose expansion) with Sponsor approval.\n- 10. Active viral infection within 1 week of Screening or ongoing bacterial or fungal infection requiring hospitalization or intravenous antimicrobials, or any other ongoing infection that would have a significant impact on safety or trial conduct per Investigator or Sponsor judgement.\n- 2. Prior CAR-T treatment within 3 months of Screening, or ≥ Grade 3 ICAHT associated with prior CAR-T treatment. Note: ICAHT per EHA/EBMT recommendation, Grade 3: ANC ≤ 0.1 × 10^9 /L for 7 days, or ANC ≤ 0.5 × 10^9 /L for 14 days, or ANC ≤ 0.5 × 10^9 /L 30 days after the CAR-T administration or later.\n- 3. Hematological autologous hematopoietic stem cell transplantation within 3 months.\n- 4. Prior allogeneic hematopoietic stem cell transplantation or solid organ transplant.\n- 5. Prior therapy with dual CD19/CD20 targeting CAR-T.\n- 6. Known severe hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in trial.\n- 7. History of graft versus host disease (GvHD) or post-transplant lymphoproliferative disorder.\n- 8. Presence of autoantibodies against La/SS-B or presence or history of autoimmune diseases associated with such antibodies.\n- 9. History of other malignancy that could affect compliance with the protocol or interpretation of results, excluding: • History of curatively treated basal or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix at any time prior to Screening. • Low-grade, early-stage prostate cancer (Gleason score ≤ 6, Stage 1 or 2) with no requirement for therapy at any time prior to Screening. • Current adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer for 2 or more years prior to Screening. • Any other malignancy treated with curative intent and in remission without treatment for 2 years prior to Screening.\n- 11. Presence of hemorrhagic cystitis.\n- 12. Active neuro-autoimmune diseases, including MS, Guillain-Barré, ALS.\n- 13. Active or residual HBV, HCV, or syphilis.\n- 14. Active HIV disease. Individuals with positive HIV history may be included with Sponsor approval after Phase Ia dose escalation if: • Ongoing antiretroviral treatment for ≥ 6 months • Adherence to antiretroviral treatment per Investigator judgement and leading to good treatment response • Good treatment response, defined by absence of clinical symptoms (including infectious and constitutional), normal blood CD4+ count (at least 500 cells /μL), and undetected HIV RNA (≤ 50 copies /mL).\n- 15. Active or recent (within 6 months of Screening) cerebrovascular ischemia/hemorrhage, dementia, Parkinson’s disease, cerebellar disease, or autoimmune disease with CNS involvement that may impair ability to evaluate neurotoxicity or have an impact on trial safety per Sponsor or Investigator assessment.\n- 16. History of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease within 6 months of Screening with an impact on trial safety per Sponsor or Investigator assessment.\n- 17. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus) requiring systemic treatment within 1 year of Screening unless stable and not increasing safety risk per Investigator judgement and approved by the Sponsor.\n- 18. Other non-hematological toxicity from prior anti-cancer treatment that has not resolved to Grade ≤1 or baseline, except for peripheral neuropathy which is eligible up to Grade 2.\n- 19. Systemic immunosuppression within 28 days of Screening.\n- 20. Last systemic lymphoma or CLL treatment, including standard and investigational treatments, within 28 days or within 5 half-lives of Screening, whichever is shorter.\n- 21. Major surgery within 14 days of Screening.\n- 22. Local radiation within 28 days of Screening.\n- 23. Live vaccination within 28 days of Screening.\n- 24. Pregnant or breastfeeding. Note: Any period mentioned before Screening (i.e., within xx days/week “of Screening”) means time before the last day of Screening period (eligibility confirmation date by the Sponsor or delegate)."}

Primary endpoints

• {"endpoint_text":"- Phase Ia: Incidence of adverse events (AEs) defined as dose-limiting toxicity (DLTs)","definition_or_measurement_approach":"Incidence of AEs defined as DLTs (no further DLT definition provided in the extracted record)."}
• {"endpoint_text":"- Phase Ib: Incidence, type, and severity of all AEs, treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II: Complete response rate (CRR) through and including the Week 13 assessment visit","definition_or_measurement_approach":"CRR assessed through and including the Week 13 assessment visit."}

Secondary endpoints

• {"endpoint_text":"- Phase Ia: Incidence, type and severity of all AEs, TEAEs, TRAEs, and SAEs including DLTs; Define recommended dose(s) for Phase Ib","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase Ia: CRR (including complete response with incomplete hematological recovery (CRi) in chronic lymphocytic leukemia (CLL)) through and including the Week 13 assessment; Duration of response (DOR)","definition_or_measurement_approach":"CRR assessed through Week 13; DOR measured (no further details provided)."}
• {"endpoint_text":"- Phase Ia: PK parameters of CAR-T (peak expansion, area under the concentration-time curve (AUC), persistence)","definition_or_measurement_approach":"PK parameters include peak expansion, AUC, and persistence in peripheral blood."}
• {"endpoint_text":"- Phase Ia: MRD levels in responding patients","definition_or_measurement_approach":"MRD levels measured in responding patients (method not specified)."}
• {"endpoint_text":"- Phase Ia: Incidence of antidrug antibody (ADA)1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR extracellular domain (ECD) of Allo-QuadCAR01-T","definition_or_measurement_approach":"Incidence of ADA1 and ADA2 formation (assay details not provided)."}
• {"endpoint_text":"- Phase Ia: Enumeration of host PB B-cell, T cell, and NK-cell numbers","definition_or_measurement_approach":"Enumeration in peripheral blood (method not specified)."}
• {"endpoint_text":"- Phase Ib: CRR through and including the Week 13 assessment","definition_or_measurement_approach":"CRR assessed through Week 13."}
• {"endpoint_text":"- Phase Ib: • DOR on trial • Partial response rate (PRR) through and including the Week 13 assessment • Overall response rate (ORR) through and including the Week 13 assessment • Progression free survival (PFS) • Time to next treatment (TTNT) • Overall survival (OS)","definition_or_measurement_approach":"Endpoints measured on-trial; time-to-event endpoints (PFS, TTNT, OS) measured per standard definitions (specifics not provided)."}
• {"endpoint_text":"- Phase Ib: PK parameters of CAR-T (peak expansion, AUC, persistence)","definition_or_measurement_approach":"PK parameters include peak expansion, AUC, and persistence in peripheral blood."}
• {"endpoint_text":"- Phase Ib: MRD levels in responding patients","definition_or_measurement_approach":"MRD levels measured in responding patients (method not specified)."}
• {"endpoint_text":"- Phase Ib: Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T","definition_or_measurement_approach":"Incidence of ADA1 and ADA2 formation (assay details not provided)."}
• {"endpoint_text":"- Phase Ib: Enumeration of host PB B-cell, T cell, and NK cell numbers","definition_or_measurement_approach":"Enumeration in peripheral blood (method not specified)."}
• {"endpoint_text":"- Phase II: Incidence, type, and severity of all AEs, TEAEs, TRAEs, and SAEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II: • DOR • PRR through and including the Week 13 assessment visit • ORR through and including the Week 13 assessment visit • PFS • TTNT • OS","definition_or_measurement_approach":"Clinical response rates through Week 13; time-to-event endpoints as listed."}
• {"endpoint_text":"- Phase II: PK parameters of CAR-T (peak expansion, AUC, persistence)","definition_or_measurement_approach":"PK parameters include peak expansion, AUC, and persistence in peripheral blood."}
• {"endpoint_text":"- Phase II: MRD levels in responding patients","definition_or_measurement_approach":"MRD levels measured in responding patients (method not specified)."}
• {"endpoint_text":"- Phase II: Incidence of ADA1 formation against anti-CD19/CD20 ECD and ADA2 formation against the RevCAR ECD of Allo-QuadCAR01-T","definition_or_measurement_approach":"Incidence of ADA1 and ADA2 formation (assay details not provided)."}
• {"endpoint_text":"- Phase II: Enumeration of host PB B-cell, T cell, and NK cell numbers","definition_or_measurement_approach":"Enumeration in peripheral blood (method not specified)."}

Germany

Earliest CTIS Part Ii Submission Date

15-09-2025

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

191

Number Of Sites

8

Number Of Participants

60

Primary sponsor

Full Name

Avencell Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States