Bispecific CAR T Cells for B-cell Malignancies (BaseCAR-01 Trial)

NCT07166549 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2025-01562, th23Holbro
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to provide locally produced, bispecific CD19 CD20 CAR T cells to patients with B-cell lymphoma/leukemia who have no access to commercial CAR T cells or who have relapsed thereafter. The primary objective is to assess the safety of bispecific anti-CD19, anti- CD20 CAR T cell-therapies after lymphodepleting chemotherapy in patients with B cell malignancies with exhausted standard treatment options.

Conditions

B-cell Leukemia; B Cell Lymphoma; Bispecific Chimeric Antigen Receptor (CAR) T Cells; Relapsed or Refractory (r/r) B-cell Malignancies; B Cell Malignancies

Keywords

Bispecific anti-CD19, anti-CD20 CAR T cell therapy; lymphapheresis; lymphodepleting (non- myeloablative) chemotherapy; Immune effector cell-associated neurotoxicity syndrome (ICANS); Cytokine release syndrome (CRS); Immune effector cell-associated haematotoxicity (ICAHT); European Group for Blood and Marrow Transplantation (EBMT); 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG); positron emission computed tomography (PET CT); acute lymphocytic leukemia (ALL); immunoglobulin heavy chain (IGH); non-Hodgkin's lymphoma (NHL); Eastern Cooperative Oncology Group (ECOG)

Outcome Measures

Primary Outcomes (4)

• Evaluation of Adverse Events

  All adverse events will be assessed in a structured manner (time of onset, duration, resolution, action been taken, assessment of intensity, relationship with study treatment), using the CTCAE Version v5.0.

  up to 3 months after CAR T cell infusion

• Evaluation of Adverse Events of special interest (CRS)

  All adverse events of special interest (CRS) will be assessed in a structured manner (time of onset, duration, resolution, action been taken, assessment of intensity, relationship with study treatment), using the ASTCT CRS Consensus Grading (Grade 1 up to Grade 4; with Grade 4 as most severe CRS Grade)

  up to 3 months after CAR T cell infusion

• Evaluation of Adverse Events of special interest (ICANS)

  All adverse events of special interest (ICANS) will be assessed in a structured manner (time of onset, duration, resolution, action been taken, assessment of intensity, relationship with study treatment), using the Immune-effector Cell-associated Encephalopathy (ICE) test, which was developed to provide objectivity for screening and grading the severity of ICANS. The ICE score is performed at least every 8 hours during in-patient care and at every outpatient visit. A higher score indicates better cognitive function, with a perfect score of 10 signifying no impairment.

  up to 3 months after CAR T cell infusion

• Evaluation of Adverse Events of special interest (ICAHT)

  Evaluation of Adverse Events of special interest (ICAHT) will be assessed in a structured manner (time of onset, duration, resolution, action been taken, assessment of intensity, relationship with study treatment), using the EHA/EBMT consensus grading. The EHA/EBMT consensus grading score is a classification system based on depth and duration of neutropenia.

  up to 3 months after CAR T cell infusion

Secondary Outcomes (8)

• Objective response rate (ORR): Change in metabolic response in FDG-PET/CT scan

  1, 3, 6 and 12 months after CAR T cell infusion

• Objective response rate (ORR): Change in minimal residual disease (MRD) negativity in blood

  1, 3, 6 and 12 months after CAR T cell infusion

• Objective response rate (ORR): Change in minimal residual disease (MRD) negativity in bone marrow

  1, 3, 6 and 12 months after CAR T cell infusion

• Objective response rate (ORR): Change in sustained MRD-negative Complete Remission (CR)

  1, 3, 6 and 12 months after CAR T cell infusion

• Progression-free survival

  up to 12 months after CAR T cell infusion

Study Arms (1)

Experimental Intervention: Bispecific anti-CD19, anti-CD20 CAR T cells

EXPERIMENTAL

Bispecific anti-CD19, anti-CD20 CAR T cells administration

Drug: Experimental Intervention

Interventions

Experimental Intervention DRUG

The study intervention includes: * Lymphapheresis * Lymphodepleting chemotherapy * CAR-T infusion Lymphocytes will be collected from the patients by lymphapheresis to produce a personalized IMP, bispecific anti-CD19, anti-CD20 CAR T cells, which will be manufactured at the GMP facility of the University Hospital Basel. Patients receive a preparative lymphodepleting chemotherapy of intravenous cyclophosphamide and fludarabine from day -5 until day -3 (or Bendamustine on day -3 and day -2), before anti-CD19/20 CAR T cells are infused (day 0 = day of infusion). Participants will undergo lymphapheresis 2-8 weeks prior to CAR T cell infusion.

Experimental Intervention: Bispecific anti-CD19, anti-CD20 CAR T cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Diagnosis of B-cell NHL or B-ALL with relapsed, refractory disease and no available standard therapeutic options (including commercially accessible CAR T products), including:
• Acute B-lymphoblastic leukaemia
• Burkitt lymphoma
• Primary CNS lymphoma
• DLBCL or high-grade lymphoma of any subtype
• Primary mediastinal B cell lymphoma (including grey zone lymphoma)
• Mantle Cell lymphoma
• Low-grade B-cell NHLs: Follicular lymphoma, chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma (SLL), marginal zone lymphoma, hairy cell leukaemia, splenic B-cell lymphoma/leukaemia with prominent nucleoli, and lymphoplasmacytic lymphoma
• CD19 and/or CD20 positive disease on most recent evaluation (by immunohistochemistry or flow cytometry)
• ECOG clinical performance status ≤2
• Able to provide written informed consent.
• Adequate organ function and bone marrow reserve, unless clearly caused by lymphoma and considered reversible, defined as:
• Adequate hepatic function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤3.0 × (ULN) and serum bilirubin ≤2.0 × ULN (except in congenital hyperbilirubinemia, such as Gilbert syndrome, where direct bilirubin ≤3.0 × ULN is allowed)
• Adequate renal function: creatinine clearance ≥30 mL/min/1.73 m2

You may not qualify if:

• Requirement for systemic corticosteroids, i.e. ≥20 mg of prednisone or equivalent daily. Other immunosuppressive drugs
• Uncontrolled coronary artery disease or uncontrolled arrhythmias
• Stroke within the previous 6 months, a history of neurodegenerative disorder or overt clinical evidence of dementia or altered mental status.
• Seizure within 6 months of signing the ICF unless related to the primary disease (e.g. CNS lymphoma).
• Active secondary malignancy that progressed or required treatment in the last 24 months, other than basal or squamous cell carcinomas of the skin. Further allowed exceptions are: Non-muscle-invasive bladder cancer, non-invasive cervical cancer, or other malignancy that is considered cured or to have a minimal risk of recurrence (e.g. a history of localized prostate or localized and treated breast cancer).
• Uncontrolled active bacterial, fungal, or viral infections, particularly active hepatitis B, hepatitis C, or HIV infection.
• Contraindications, known life-threatening allergies, hypersensitivity, or intolerance to any of the study treatments, including previous severe reactions to dimethyl-sulfoxide
• Cytotoxic chemotherapy within 14 days before apheresis collection for CAR-T cells, respectively 12 weeks for Bendamustin and Fludarabine, and 6 months for Alemtuzumab and ATG.
• Cytotoxic chemotherapy (except for lymphodepletion) within 14 days of CAR-T cell infusion.
• Patients who have undergone allogeneic hematopoietic stem cell transplantation less than 12 weeks ago, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
• Previous CAR-T cell therapy within 12 weeks of planned CAR-T cell infusion.
• Investigational treatments within other trials ≤ 4 weeks before enrollment.
• Lack of safe contraception; Women who are pregnant or breastfeeding; and men who plan to father a child while enrolled in this study within 1 year of receiving bispecific anti-CD20, anti-CD19 CAR T cells.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Division of Hematology or Medical Oncology

Basel, Canton of Basel-City, 4031, Switzerland

Location

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, B-Cell; Recurrence; Cytokine Release Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation; Shock

Study Officials

• Andreas Holbro, Prof. Dr.

  University Hospital Basel, Division of Hematology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Holbro, Prof. Dr.

CONTACT

+41 61 556 56 47; andreas.holbro@usb.ch

Jana van den Berg, Dr. med

CONTACT

Jana.VandenBerg@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 10, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: December 24, 2025

Record last verified: 2025-12

Locations

CH (1)