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.
Chimeric antigen receptor (CAR) T cells are engineered T-lymphocytes with artificial receptors, containing domains of a T cell receptor as well as a B cell receptor with predefined specificity to a target antigen. In patients with relapsed or refractory (r/r) B-cell malignancies, who would otherwise have a poor prognosis, CD19-directed CAR T cell therapy showed high response rates. A common cause of relapse is loss of the target antigen on the tumor cells, e.g. CD19. In such cases, further approved treatment options are very limited to date, but recent preclinical and early clinical studies have shown that bispecific anti-CD19, anti-CD20 CAR T cells can overcome this hurdle, adding a second target and leading to excellent outcomes in heavily pretreated patients. 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. A secondary objective is the assessment of efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
University Hospital Basel, Division of Hematology or Medical Oncology
Basel, Canton of Basel-City, Switzerland
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.
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: up to 3 months after CAR T cell infusion
Objective response rate (ORR): Change in metabolic response in FDG-PET/CT scan
For lymphomas and B-cell ALL with lymphadenopathy metabolic response in FDG-PET/CT scan according to the Lugano Classification (Response assessment: Complete Remission; Partial Remission; Progressive Disease)
Time frame: 1, 3, 6 and 12 months after CAR T cell infusion
Objective response rate (ORR): Change in minimal residual disease (MRD) negativity in blood
For patients with B-cell ALL minimal residual disease (MRD) negativity as determined by flow cytometry
Time frame: 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
For patients with B-cell ALL minimal residual disease (MRD) negativity as determined by flow cytometry
Time frame: 1, 3, 6 and 12 months after CAR T cell infusion
Objective response rate (ORR): Change in sustained MRD-negative Complete Remission (CR)
For patients with B-cell ALL: Sustained MRD-negative CR determined by polymerase chain reaction of the IgH rearrangement
Time frame: 1, 3, 6 and 12 months after CAR T cell infusion
Progression-free survival
Progression-free survival, defined as the time between infusion of CAR T product to progression or death, whichever occurs first
Time frame: up to 12 months after CAR T cell infusion
Event free survival
Event free survival, defined as time between infusion of CAR T product to not achieving complete remission 3 months after CAR T infusion, progression, or death, whichever occurs first.
Time frame: up to 3 months after CAR T cell infusion
Overall survival
Overall survival, defined as the time between the day of infusion of CAR T product to death of any cause.
Time frame: up to 12 months after CAR T cell infusion
Cumulative incidence of non-relapse mortality
Cumulative incidence of non-relapse mortality, defined as any death not related to underlying lymphoid malignancy.
Time frame: up to 12 months after CAR T cell infusion
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