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

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ClinicalTrials.gov Identifier: NCT04450069
Recruitment Status : Recruiting
First Posted : June 29, 2020
Last Update Posted : December 14, 2020
Sponsor:
Information provided by (Responsible Party):
Calibr, a division of Scripps Research

Tracking Information
First Submitted Date  ICMJE June 23, 2020
First Posted Date  ICMJE June 29, 2020
Last Update Posted Date December 14, 2020
Actual Study Start Date  ICMJE August 14, 2020
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2020)
  • Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events [ Time Frame: 35 days ]
    To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
  • Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: up to 1 year ]
    Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2020)
  • Maximum drug concentration (Cmax) of SWI019 [ Time Frame: up to Day 35 ]
    To determine the maximum concentration of SWI019 in a patient's peripheral blood
  • Area under the curve (AUC) of SWI019 [ Time Frame: up to Day 35 ]
    To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
  • Time to reach Cmax (Tmax) of SWI019 [ Time Frame: up to Day 35 ]
    To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
  • Clearance (CL) of SWI019 [ Time Frame: up to Day 35 ]
    To determine the clearance factor of SWI019 in a patient's peripheral blood
  • Apparent elimination half-life (t1/2) of SWI019 [ Time Frame: up to Day 35 ]
    To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
  • Quantification of CLBR001 cells in peripheral blood [ Time Frame: up to 1 year ]
    To quantify CLBR001 in a patient's peripheral blood at different time points
  • Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies [ Time Frame: up to 1 year ]
    To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
  • Immunogenic response to CLBR001 [ Time Frame: up to 1 year ]
    To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
  • Immunogenic response to SWI019 [ Time Frame: up to 1 year ]
    To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
  • Serum cytokine concentrations [ Time Frame: up to 1 year ]
    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
  • Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria [ Time Frame: up to 1 year ]
    To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
  • Duration of response (DOR) [ Time Frame: up to 1 year ]
    To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
  • Progression free survival (PFS) [ Time Frame: up to 1 year ]
    To evaluate the duration of patient's progression-free survival
  • Overall survival (OS) [ Time Frame: up to 1 year ]
    To evaluate the overall duration of patient's survival
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2020)
  • Maximum drug concentration (Cmax) of SWI019 [ Time Frame: up to Day 35 ]
    To determine the maximum concentration of SWI019 in a patient's peripheral blood
  • Area under the curve (AUC) of SWI019 [ Time Frame: up to Day 35 ]
    To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time
  • Time to reach Cmax (Tmax) of SWI019 [ Time Frame: up to Day 35 ]
    To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood
  • Clearance (CL) of SWI019 [ Time Frame: up to Day 35 ]
    To determine the clearance factor of SWI019 in a patient's peripheral blood
  • Apparent elimination half-life (t1/2) of SWI019 [ Time Frame: up to Day 35 ]
    To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood
  • Quantification of CLBR001 cells in peripheral blood [ Time Frame: up to 1 year ]
    To quantify CLBR001 in a patient's peripheral blood at different time points
  • Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies [ Time Frame: up to 1 year ]
    To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry
  • Immunogenic response to CLBR001 [ Time Frame: up to 1 year ]
    To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood
  • Immunogenic response to SWI019 [ Time Frame: up to 1 year ]
    To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood
  • Serum cytokine concentrations [ Time Frame: up to 1 year ]
    To measure the cytokine levels in a patient's peripheral blood at different time points
  • Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria [ Time Frame: up to 1 year ]
    To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria
  • Duration of response (DOR) [ Time Frame: up to 1 year ]
    To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
  • Progression free survival (PFS) [ Time Frame: up to 1 year ]
    To evaluate the duration of patient's progression-free survival
  • Overall survival (OS) [ Time Frame: up to 1 year ]
    To evaluate the overall duration of patient's survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CLBR001 and SWI019 in Patients With Relapsed / Refractory B-cell Malignancies
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Combination Product: CLBR001 and SWI019
Investigational immunotherapy for B cell malignancies
Study Arms  ICMJE Experimental: Dose Escalation
CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)
Intervention: Combination Product: CLBR001 and SWI019
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2020)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2024
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pamela Garzone, Ph.D. 858-242-1072 pgarzone@scripps.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04450069
Other Study ID Numbers  ICMJE CBR-sCAR19-3001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Calibr, a division of Scripps Research
Study Sponsor  ICMJE Calibr, a division of Scripps Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Carolyn Mulroney, MD University of California, San Diego
PRS Account Calibr, a division of Scripps Research
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP