clbr001 and swi019 in patients with relapsed / refractory b-cell malignancies

Conditions: Relapsed/Refractory B-cell Lymphomas; Diffuse Large B Cell Lymphoma (DLBCL); Follicular Lymphoma (FL); Chronic Lymphocytic Leukemia (CLL); Marginal Zone Lymphoma (MZL); Mantle Cell Lymphoma; Small Lymphocytic Lymphoma (SLL); Primary Mediastinal Large B Cell Lymphoma; Transformed Follicular Lymphoma; Waldenstrom Macroglobulinemia; Lymphoplasmacytic Lymphoma; Burkitt Lymphoma

Summary: clbr001 + swi019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with b cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. this first-in-human study will assess the safety and tolerability of clbr001 + swi019 and is designed to determine the maximum tolerated dose (mtd) or optimal swi019 dose (osd). patients will be administered a single infusion of clbr001 cells followed by cycles of swi019. the study will also assess the pharmacokinetics and pharmacodynamics of clbr001 + swi019.

clbr001 + swi019 is a two-component therapy comprising an autologous chimeric antigen receptor t (car-t) cell product (clbr001, the switchable car-t cell (scar-t)) and an anti-cd19 (cluster of differentiation antigen 19) antibody (swi019, the switch, a biologic). in combination, swi019 acts as an adapter molecule that controls the activity of the clbr001 car-t cell product.

Eligibility criteria:
inclusion criteria: * patients with relapsed / refractory previously treated b cell malignancies (according to the world health organization classification; 2017) * patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-containing chemotherapy, anti-cd20 (cluster of differentiation antigen 20) therapies and/or brutton's tyrosine kinase (btk) inhibitors * patients treated with prior cd19 targeted molecules (e.g., blincyto) must have confirmed cd19+ disease * patients must be ineligible for allogeneic stem cell transplant (sct) * eastern cooperative oncology group (ecog) performance status (ps) 0 or 1 * estimated life expectancy of ≥ 12 weeks from the first day of swi019 dose administered * willing to undergo pre- and post-treatment core needle biopsy * adequate hematological, renal, pulmonary, cardiac, and liver function * resolved adverse events of any prior therapy to either baseline or ctcae grade ≤1 * women of childbearing potential, a negative pregnancy test and must agree to practice effective birth control * men sexually active with female partners of child bearing potential must agree to practice effective contraception * willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures exclusion criteria: * patients diagnosed with certain disease histologies including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance (mgus), t-cell histiocyte large b cell lymphoma * pregnant or lactating women * active bacterial, viral, and fungal infections * history of allogeneic stem cell transplantation * treatment with any prior lentiviral or retroviral based car-t * patients receiving live (attenuated) vaccines within 4 weeks of screening visit or need for live vaccine on study * patients with known active central nervous system (cns) disease. patients with prior cns disease that has been effectively treated may be eligible * history of class iii or iv new york heart association (nyha) heart failure, myocardial infarction, unstable angina or other significant cardiac disease within 6 months of screening * involvement of cardiac tissue by lymphoma * uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (itp) * hiv-1 and hiv-2 antibody positive patients

Keywords: car-t cell therapy switchable car-t cell autologous cell therapy cd19 positive disease cd19 car-t cell blood cancer hematological malignancy neoplasms