p-bcma-101 tscm car-t cells in the treatment of patients with multiple myeloma (mm)

Conditions: Multiple Myeloma

Summary: phase 1 of the study is comprised of an open-label, single ascending dose (sad), multiple cohort study; a multiple dose cycle administration cohort study; and a combination administration study of p-bcma-101 autologous t stem cell memory (tscm) car-t cells in patients with relapsed / refractory mm. followed by a phase 2, open-label, efficacy and safety study. rimiducid may be administered as indicated.

phase 1 follows a 3 + 3 design of dose-escalating cohorts. phase 2 of the study is an open-label multi-center efficacy and safety study. after a patient enrolls, leukapheresis will be performed to obtain peripheral blood mononuclear cells which will be sent to a manufacturing site to produce p-bcma-101 car-t cells. the cells will then be returned to the investigational site and, after a standard chemotherapy based conditioning regimen, will be administered to the patient across 1-3 infusions, with or without combination therapy. treated patients will undergo serial measurements of safety, tolerability and response. rimiducid may be administered as indicated.

Eligibility criteria:
inclusion criteria: * males or females, ≥18 years of age * must have a confirmed diagnosis of active mm * must have measurable mm * must have relapsed / refractory mm, having received treatment with proteasome inhibitor and imid \[phase 2: must have relapsed / refractory mm, and refractory to last line of therapy, having received treatment with proteasome inhibitor, an imid, cd38 targeted therapy and undergone autologous stem cell transplant (asct) or not a candidate for asct.\] * must have adequate hepatic, renal, cardiac and hematopoietic function exclusion criteria: * is pregnant or lactating * has inadequate venous access and/or contraindications to leukapheresis * has active hemolytic anemia, plasma cell leukemia, waldenstrom's macroglobulinemia, poems syndrome, disseminated intravascular coagulation, leukostasis, amyloidosis, significant autoimmune, cns or other malignant disease * has an active second malignancy (not disease-free for at least 5 years) in addition to mm, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma. * has active autoimmune disease * has a history of significant central nervous system (cns) disease, such as stroke, epilepsy, etc. * has an active systemic infection * has hepatitis b or c virus, human immunodeficiency virus (hiv), or human t-lymphotropic virus (htlv) infection, or any immunodeficiency syndrome. * has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol * has receiving immunosuppressive or other contraindicated therapies within the excluded time frame from entry * has cns metastases or symptomatic cns involvement * has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days. * unable to take acetylsalicylic acid (asa) daily as prophylactic anticoagulation. (cohorts r and rp only). * history of thromboembolic disease within the past 6 months, regardless of anticoagulation (cohorts r and rp only).

Keywords: car-t cells