💬In plain words
What the trial is, and whether it could suit you
This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, with fludarabine and cyclophosphamide lymphodepletion, for the treatment of patients with B-cell hematologic malignancies that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). BAFFR-based chimeric antigen receptor T-cells is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* PRE-REGISTRATION: Age ≥ 18 years
* PRE-REGISTRATION: Confirmed diagnosis of 1 of the following relapsed or refractory B-cell hematologic malignancies: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or large B cell lymphoma (LBCL) including Richter's transformation from CLL/SLL
* For CD19+ B cell malignancies; relapsed or refractory disease is defined by one of the following histopathology:
* Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory disease is defined as:
* Demonstration of progressive or stable disease by positron emission tomography/computed tomography (PET/CT) or computed tomography (CT) criteria according to the international workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria
* Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease is defined as:
* Demonstration of progressive or stable disease by PET/CT or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma
* PRE-REGISTRATION: Disease Specific prior lines of therapies below:
* For CLL/SLL, patients must have received ≥ two prior lines of therapy, and/or ≥ 6 months of second line prior BTK inhibition (e.g. ibrutinib or other such as acalabrutinib or zanubrutinib) and must have failed to respond to venetoclax or be intolerant. Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cγ2) may be included even if on ibrutinib therapy for less than 6 months
* These patients may or may not have received prior antibody directed against cluster of differentiation 20 (CD20).
* For Follicular Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
* NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen receptor T-cell therapy (CART) must have a 100-day washout period.
* For Mantle Cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20, and a BTK inhibitor.
* NOTE: Prior CD19 directed CART must have a 100-day washout period.
* For Marginal Zone Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
* NOTE: Prior CD19 directed CART must have a 100-day washout period.
* For Large B cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20. Prior exposure to CD19 directed CART will be allowed at the discretion of the Principal Investigator.
* NOTE: Prior failed CD19 directed CART must have a 100-day washout period
* For Richter's Transformation, patients must have received ≥two prior lines of therapy, including an antibody directed against CD20.
* 100-day washout period starts from the date of the last prior CAR-T infusion.
* PRE-REGISTRATION: Measurable disease
* REGISTRATION: Positive BAFFR test
* REGISTRATION: Measurable disease
* REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* REGISTRATION: Hemoglobin ≥ 9.0 g/dL (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
* REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
* REGISTRATION: Platelet count ≥100,000/mm\^3 (unless due to documented marrow involvement with disease) obtained ≤ 14 days prior to registration
* REGISTRATION: Total bilirubin ≤ 1.5 x upper limits of normal (ULN) (Subjects with Gilbert's Syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) obtained ≤ 14 days prior to registration
* REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) obtained ≤ 14 days prior to registration
* REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR) /activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy obtained ≤ 14 days prior to registration
* Patients on a stable, maintenance regimen of anticoagulant therapy for ≥ 30 days prior to registration may have PT/INR measurements \> 1.5 X ULN if, in the judgment of the investigator, the patient is suitable for the study
* REGISTRATION: Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula obtained ≤ 14 days prior to registration
* REGISTRATION: Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* REGISTRATION: Provide written informed consent understand and comply with protocol-required study procedures
* REGISTARTION: Patients must have an ejection fraction (EF) of ≥ 45%
* REGISTRATION: Patients must have pulse ox measurements of \> 92% on room air
* REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
* REGISTRATION: Willing to return to enrolling institution for study follow-up
Exclusion Criteria:
* PRE-REGISTRATION: Prior solid organ transplantation
* PRE-REGISTRATION: Unstable angina, clinically significant arrhythmia, or myocardial infarction ≤ 6 months of prior to pre-registration, or grade 3 or higher pericardial effusion at the time of pre-registration
* PRE-REGISTRATION: Prior anti-BAFF-R therapies
* PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy
* PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent ≤ 14 day