Study of CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell
Condition: Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase 1/1b, interventional single arm, open label, treatment study designed to
      evaluate the safety and feasibility of infusion of autologous T cells engineered to contain
      an anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20)
      single chain variable fragment (scFv) coupled to cluster of differentiation CD3ζ (CD3ζ) and
      co-stimulatory domain 4-1BB (4-1BB) signaling domains in patients with relapsed and/or
      refractory CD19 or CD20 positive B cell malignancies
    

Detailed description: 
      This is a single center, single arm, open label phase I/1b study to demonstrate the
      feasibility of manufacturing CAR-T cells expressing tandem receptors against both CD20 and
      CD19 (CAR-20/19-T) in a completely closed system using the CliniMACS Prodigy device and then
      determine the safety of this dual targeted CAR in a first-in-human study of patients with
      relapsed and refractory B cell malignancies. Secondary outcomes will include response rates,
      and observed toxicities of the treatment, specifically the development of cytokine release
      syndrome (CRS), an inflammatory storm that has been seen with previous CAR-T therapies.
    

Intervention name(s): CAR-20/19-T cells (1.0 x10^5 CAR-20/19-T cells/kg); CAR-20/19-T cells (2.5 x10^5 CAR-20/19-T cells/kg); CAR-20/19-T cells (7.5 x10^5 CAR-20/19-T cells/kg); CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 0: 2.5 x10^5 CAR-20/19-T cells/kg (starting dose level); CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 1: 7.5 x10^5 CAR-20/19-T cells/kg; CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Phase 1 Dose Level 2: 2.5 x10^6 CAR-20/19-T cells/kg (goal cell dose)
Phase 1b Expansion Dose Level: 2.5 x 10^6 cells/kg (single infusion); CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: The study is divided into two phases. Phase 1 and Phase 1b. Phase 1: consists of 2 cohorts; dose escalation and dose expansion. The CAR-T cells were given over 2 days.
In the phase 1 portion, there will be a dose escalation cohort to determine the safe CAR-20/19-T cell dose in patients with CLL/SLL and NHL. Once the desired dose has been identified there will be a 6 patient dose expansion phase at the specified dose level.
Phase 1b: In the Phase 1b portion of the study, we will test the safety of unfractionated CAR-T cells utilizing the safe dose identified in the phase 1 portion (2.5 x 10^6 cells/kg).
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CAR-T; Chimeric antigen receptor T-cell therapy; CAR Therapy