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Clinical Trial 20493

Cancer Type: Immunotherapy
Study Type: Treatment
NCT#: NCT03960840

Phase: Phase I
Prinicipal Investigator: Pinilla-Ibarz, Javier

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Overview

Study Title

Phase I, Open Label, Multicenter, Dose Escalation Study of YTB323 in Adult Patients with CLL/SLL and DLBCL

Summary

This is a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a CD19-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells will be investigated in combination with ibrutinib in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and as single agent in diffuse large B-cell lymphoma (DLBCL) and in adult acute lymphoblastic leukemia (ALL).

Objective

Primary Objectives (CLL/SLL and DLBCL): -Identify the Recommended Dose (RD) of YTB323 and characterize the safety of YTB323 in combination with Ibrutinib in CLL/SLL and as single agent in DLBCL. -Characterize Ibrutinib tolerability in combination with YTB323 in CLL/SLL -Evaluate feasibility of manufacturing process Secondary Objectives (CLL/SLL and DLBCL): -Characterize the in vivo cellular kinetics of YTB323 in peripheral blood, bone marrow, and lymph nodes by quantitative polymerase chain reaction (qPCR) -Characterize the incidence and prevalence of pre-existing and treatment induced immunogenicity (cellular and humoral) of YTB323 Secondary Objectives (CLL/SLL): -Assess antitumor activity of YTB323 in combination with Ibrutinib in CLL as assessed by local investigator Secondary Objective (DLBCL): -Assess antitumor activity of YTB323 single agent in DLBCL as assessed by local investigator Exploratory Objectives (CLL/SLL and DLBCL): -Further characterize antitumor activity by assessing the progression-free survival (PFS) -Characterize the in vivo cellular kinetics of YTB323 in peripheral blood, bone marrow, and lymph nodes as measured by flow cytometry -Explore the correlation of blood and/or tissue exposure (e.g. bone marrow, lymph nodes, and others if available) with clinical end points -Describe the composition of circulating immune cells and T-cell subsets (immunophenotyping in peripheral blood), summarized by clinical response -Identify potential predictive markers of response/resistance -Assess blood/bone marro MRD negative response rate -Assess potential markers in tumor samples and circulating tumor DNA that may correlate with response and/or resistance (gene expression, mutational evolution, minimal residual disease) -Assess relationship of soluble immune factors and molecular characteristics of YTB323 leukapheresis product/final product of YTB323 with cellular kinetics, safety and efficacy -Assess relationship between vital sign, physical activity parameters, CRS and neurotoxicity Exploratory Objectives (CLL/SLL): -Assess blood/bone marrow MRD negative response rate -Characterize the potential impact of YTB323 on Ibrutinib PK -Assess impact of BTK & PLCγ2 mutations on antitumor response

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

748645 (Ibrutinib); Ibrutinib (Imbruvica); PCI-32765 (Ibrutinib); YTB323 ()

Inclusion Criteria

Inclusion Criteria:

  • ECOG performance status 0-1
  • CLL or SLL diagnosis according to iwCLL criteria
  • CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or subsequent line of therapy
  • DLBCL diagnosis by local histopathology
  • DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous hematopoietic stem cell transplantation (HSCT)
  • Refractory or relapsed CD19-positive ALL
  • ALL with morphologic disease in the bone marrow
  • Other criteria may apply

  • Exclusion Criteria

    Exclusion Criteria:

  • Prior CD19-directed therapy
  • Prior administration of a genetically engineered cellular product
  • Prior allogeneic HSCT
  • Richter's transformation
  • Active CNS lymphoma
  • Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis
  • Other criteria may apply

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