Clinical Trials /

CD19-specific CAR-T Cells in CLL/SLL and DLBCL

NCT03960840

Description:

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).

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD19-specific CAR-T Cells in CLL/SLL and DLBCL
  • Official Title: Phase I, Open Label, Multicenter, Dose Escalation Study of CD19-specific CAR-T Cells in Adult Patients With CLL/SLL and DLBCL

Clinical Trial IDs

  • ORG STUDY ID: CYTB323A12101
  • NCT ID: NCT03960840

Conditions

  • Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
YTB323 and ibrutinibCLL/SLL
YTB323 single agentDLBCL

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
CLL/SLLExperimentalDose escalation and expansion of YTB323 in combination with ibrutinib
  • YTB323 and ibrutinib
DLBCLExperimentalDose escalation and expansion of YTB323 single agent in DLBCL
  • YTB323 single agent

Eligibility 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)

        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

          -  Anti-CD20 monoclonal antibodies within 4 weeks prior to infusion
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose recommendation: incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Cellular kinetics: CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood, bone marrow and lymph nodes
Time Frame:24 months
Safety Issue:
Description:
Measure:Immunogenicity: cellular and humoral responses to the CAR transgene
Time Frame:24 months
Safety Issue:
Description:
Measure:Tumor response in CLL/SLL: CR/PR per iwCLL response criteria
Time Frame:24 months
Safety Issue:
Description:
Measure:Tumor response in DLBCL: ORR/CR/PR per Lugano criteria
Time Frame:24 months
Safety Issue:
Description:
Measure:Duration of response (DOR) in CLL/SLL and DLBCL
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • CD19 CAR-T cells, CLL, SLL, ibrutinib, DLBCL

Last Updated

January 17, 2020