Clinical Trials /

CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies

NCT04450069

Description:

CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies
  • Official Title: A Phase 1, Open-label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the Combination of CLBR001 and SWI019 in Patients With Relapsed/Refractory B-cell Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CBR-sCAR19-3001
  • NCT ID: NCT04450069

Conditions

  • Relapsed/Refractory B-cell Lymphomas
  • Diffuse Large B Cell Lymphoma (DLBCL)
  • Follicular Lymphoma (FL)
  • Chronic Lymphocytic Leukemia (CLL)
  • Marginal Zone Lymphoma (MZL)
  • Mantle Cell Lymphoma
  • Small Lymphocytic Lymphoma (SLL)
  • Primary Mediastinal Large B Cell Lymphoma
  • Transformed Follicular Lymphoma

Purpose

CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.

Detailed Description

      CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen
      receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an
      anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic).
      In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001
      CAR-T cell product.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalCLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients with relapsed / refractory previously treated B cell malignancies (according
                 to the World Health Organization classification; 2017)
    
              -  Chemotherapy-refractory disease
    
              -  Patients must have received adequate prior therapy including at least two lines of
                 prior therapies including anthracycline-containing chemotherapy, anti-CD20 (cluster of
                 differentiation antigen 20) therapies and/or Brutton's tyrosine kinase (BTK)
                 inhibitors
    
              -  Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have
                 confirmed CD19+ disease
    
              -  Patients must be ineligible for allogeneic stem cell transplant (SCT)
    
              -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
    
              -  Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered
    
              -  Willing to undergo pre- and post-treatment core needle biopsy
    
              -  Adequate hematological, renal, pulmonary, cardiac, and liver function
    
              -  Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1
    
              -  Women of childbearing potential, a negative pregnancy test and must agree to practice
                 effective birth control
    
              -  Men sexually active with female partners of child bearing potential must agree to
                 practice effective contraception
    
              -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests and
                 other procedures
    
            Exclusion Criteria:
    
              -  Patients diagnosed with disease histologies including pediatric lymphomas/leukemias,
                 Burkitt lymphoma, lymphoplasmacytic lymphomas, monoclonal gammopathy of undetermined
                 significance (MGUS), T-cell histiocyte large B cell lymphoma
    
              -  Pregnant or lactating women
    
              -  Active bacterial, viral, and fungal infections
    
              -  History of allogeneic stem cell transplantation
    
              -  Treatment with any prior CD19 or CD20 CAR-T
    
              -  Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or
                 need for live vaccine on study
    
              -  Patients with known active central nervous system (CNS) disease. Patients with prior
                 CNS disease that has been effectively treated may be eligible
    
              -  History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial
                 infarction, unstable angina or other significant cardiac disease within 6 months of
                 screening
    
              -  Involvement of cardiac tissue by lymphoma
    
              -  Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)
    
              -  HIV-1 and HIV-2 antibody positive patients
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
    Time Frame:35 days
    Safety Issue:
    Description:To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events

    Secondary Outcome Measures

    Measure:Maximum drug concentration (Cmax) of SWI019
    Time Frame:up to Day 35
    Safety Issue:
    Description:To determine the maximum concentration of SWI019 in a patient's peripheral blood
    Measure:Area under the curve (AUC) of SWI019
    Time Frame:up to Day 35
    Safety Issue:
    Description:To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
    Measure:Time to reach Cmax (Tmax) of SWI019
    Time Frame:up to Day 35
    Safety Issue:
    Description:To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
    Measure:Clearance (CL) of SWI019
    Time Frame:up to Day 35
    Safety Issue:
    Description:To determine the clearance factor of SWI019 in a patient's peripheral blood
    Measure:Apparent elimination half-life (t1/2) of SWI019
    Time Frame:up to Day 35
    Safety Issue:
    Description:To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
    Measure:Quantification of CLBR001 cells in peripheral blood
    Time Frame:up to 1 year
    Safety Issue:
    Description:To quantify CLBR001 in a patient's peripheral blood at different time points
    Measure:Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
    Measure:Immunogenic response to CLBR001
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
    Measure:Immunogenic response to SWI019
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
    Measure:Serum cytokine concentrations
    Time Frame:up to 1 year
    Safety Issue:
    Description:To measure the cytokine levels (e.g. TNFa, IL-6, IL-1, IL-2, etc.) in a patient's peripheral blood at different time points
    Measure:Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria
    Time Frame:up to 1 year
    Safety Issue:
    Description:To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
    Measure:Duration of response (DOR)
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
    Measure:Progression free survival (PFS)
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the duration of patient's progression-free survival
    Measure:Overall survival (OS)
    Time Frame:up to 1 year
    Safety Issue:
    Description:To evaluate the overall duration of patient's survival

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Calibr, a division of Scripps Research

    Trial Keywords

    • CAR-T Cell Therapy
    • Switchable CAR-T Cell
    • Autologous Cell Therapy
    • CD19 Positive Disease
    • CD19 CAR-T Cell
    • Blood Cancer
    • Hematological malignancy
    • Neoplasms

    Last Updated

    August 28, 2020