B Cell Lymphomas Clinical Trial
Official title:
Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells in Pediatric Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
This is a single center, single arm, open-label pilot study to determine the feasibility and safety of a single dose administered as spilt fractions of autologous T cells expressing CD22 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART22" cells) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
The study will consist of three sequential phases: 1) a screening phase, 2) a manufacturing and pre- treatment phase, consisting of apheresis (if applicable) and chemotherapy (if applicable), and 3) a treatment phase, consisting of a CART22 transfused cell infusion and follow up evaluations. After signing informed consent, patients will undergo screening tests and procedures to determine eligibility. Once patient eligibility is confirmed, patients will have cells collected by leukapheresis to obtain peripheral blood mononuclear cells (PBMC) for CART22 manufacturing, unless adequate numbers of cells are available from a prior apheresis. Cells will be transduced with the anti-CD22 TCRζ/4-1BB lentiviral vector, expanded in vitro and then frozen for future administration. Cryopreserved historical apheresis products collected from the patient prior to study entry are usable for CART22 manufacturing if collected at an appropriately certified apheresis center and the product meets adequate mononuclear cell yields. If a historical apheresis product is not available, an apheresis procedure will be scheduled for cell procurement after study entry. Unless contraindicated and medically not advisable based on previous chemotherapy, patients will be given conditioning chemotherapy prior to CART22 cell infusion with the intent of lymphodepletion. Additionally, if the patient's white blood cell (WBC) count is ≤ 1,000 /uL, conditioning/lymphodepleting chemotherapy is NOT required. The chemotherapy will be planned so that the last dose is completed 1-4 days BEFORE the planned infusion of CART22 cells. The chemotherapy start date will vary based on the duration of the selected chemotherapy regimen. If the period from chemotherapy to CART22 infusion is delayed 4 or more weeks, the patient will need to be re-treated with lymphodepleting chemotherapy prior to CART22 infusion. We will enroll 15 evaluable patients for the primary safety endpoint analysis. Primary safety evaluable patients are those who have received any CART22 cells. The first three subjects infused with CART22 will be staggered by 14 days to allow for monitoring of adverse events, including CRS. Subjects with a manufactured cell dose that is less than the protocol-specified dose will be scored as a manufacturing failure. These subjects will receive their cell infusion, provided that all other manufacturing release criteria are met. All patients will have blood tests to assess CART22 safety, engraftment and persistence at regular intervals throughout the study (Visit Evaluation Schedule in Appendix 1). Circulating CART22 T cells subsets will be assessed at various times after infusion. CART22 trafficking will be assessed in bone marrow aspirates, and other tissues, if available. Follow up is planned at a minimum of weekly for 4 weeks, monthly for 6 months, then patients will be followed quarterly for the remainder of the year to obtain a medical history, undergo a physical examination, and blood tests. Additional samples collections and assessments between schedule visits after CART22 cell infusion will be performed as clinically indicated. Following these evaluations, patients will enter a roll-over study for long term follow-up for up to an additional fourteen years to assess for safety assessments per the FDA guidelines. ;
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