This trial aims to demonstrate the feasibility of this approach to reliably generate product and to safely administer the product to patients who have B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia.
Subjects with CD19+ B-cell lymphoma or B-Cell Acute Lymphoblastic Leukemia (B-ALL) with no currently available curative treatment option (such as autologous or allogeneic Hematopoietic stem cell transplantation (HSCT)) who have a limited prognosis (<2-year projected survival) will be enrolled. Participation on this trial is permitted as a bridge to HSCT.
Peripheral blood CD3 count > 200/µL by flow cytometry. Please note that this test might need to be repeated multiple times as standard practice to optimize collection efficiency.
Subjects will have a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), CLL, Marginal Zone Lymphoma (MZL), Lymphoplasmacytic Lymphoma (LPL) or B-ALL and will have failed at least 2 lines of therapy in the case of lymphoma and one line if the diagnosis is B-ALL or be refractory (no response or progressive disease) to first line therapy. A line of therapy must include conventional (immuno) chemotherapy (e.g. rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) or Bendamustine plus Rituximab (BR) in the case of lymphoma) administered for at least 2 cycles. Second or greater lines of therapy must be administered for at least two cycles. Single agent anti-CD20 monoclonal antibody (e.g. rituximab, obinutuzumab) is not considered for the purposes of these criteria to count as a line of therapy. The definition of a line of therapy is taken according to recommended regimens for first and second line therapy in the relevant sections of the National Comprehensive Cancer Network (NCCN) guidelines. The most recent version of the guidelines will be used for eligibility determination. In the unlikely event that a subject received a first or second line regimen no longer listed in the most recent guidelines, but previously present in the version of the guidelines active at the time the therapy was administered, then the subject would be deemed to have received a line of therapy.
Subjects with pathological and clinical evidence of transformed indolent lymphoma (FL, CLL, MZL or LPL) are eligible for participation on this trial if they have received at least one line of therapy for transformed disease for at least two cycles regardless of response.
Infection with HIV (human immunodeficiency virus) and active viral replication. Patients with an undetectable viral load on ART (antiretroviral treatment) can be considered for participation on this protocol.
Infection with hepatitis B and active viral replication.
Infection with hepatitis C and active viral replication.
Active untreated CNS (central nervous system) leukemia or lymphoma. Patients with treated CNS leptomeningeal or parenchymal disease might be eligible if the CNS disease is inactive. The CSF (cerebrospinal fluid) must be clear on two separate occasions at least 4 weeks apart. Brain imaging must demonstrate no evidence of progressive disease on two separate occasions at least 4 weeks apart.
Single group
Chimeric Antigen Receptor (CAR) T-Cell Product (Autologous)
DrugThis protocol describes the use of an automated cell processor and culture system, the CliniMACS Prodigy device sold by Miltenyi Biotec, for the local manufacture of CAR T-cells targeting the CD19 antigen. The manufacturing process will use a lentiviral vector (CAR19) provided by Lentigen, a wholly owned subsidiary of Miltenyi Biotec, to transfect T-cells collected from eligible patients. Live cells will be harvested by the device after culture and infused intravenously to the patient from whom the cells were originally obtained.
Successful local CAR T-cell manufacturing
To demonstrate the feasibility of reliably producing CD19-targeted CAR T-cells at our site using the Prodigy device.
Safety of administration
To demonstrate the safety of administering the manufactured product to subjects as measured by adverse events.
Safety of administration
Cytokine Release Syndrome score
Safety of administration
Immune Effector Cell Associated Neurotoxicity Syndrome Grading for Adults (score) - A score of 10 represents no impairment, 7-9 grade 1 ICANS, 3-6 grade 2 ICANS, and 0-2 grade 3 ICANS. A score of 0 due to patient being unarousable and unable to perform assessment corresponds to grade 4 ICANS.
Response to therapy
Response evaluation according to Lugano criteria for lymphoma and NCCN guidelines for ALL.
Response to therapy
Response criteria ALL-E and for MRD (minimal residual disease) ALL-F for B-ALL.
CAR T-cell kinetics
CAR T-cell counts by flow cytometry
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John Lister
Lead sponsor
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor institution
Lentigen Technology, Inc.
Collaborator
Miltenyi Biotec, Inc.
Collaborator
Allegheny Health Network
Collaborator
