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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04450069
Other study ID # CBR-sCAR19-3001
Secondary ID
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date August 14, 2020
Est. completion date June 2024

Study information

Verified date January 2024
Source Calibr, a division of Scripps Research
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 18
Est. completion date June 2024
Est. primary completion date April 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Patients with relapsed / refractory previously treated B cell malignancies (according to the World Health Organization classification; 2017) - Patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-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 certain disease histologies including pediatric lymphomas/leukemias, 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 lentiviral or retroviral based 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

Study Design


Intervention

Combination Product:
CLBR001 and SWI019
Investigational immunotherapy for B cell malignancies

Locations

Country Name City State
United States University of Chicago Chicago Illinois
United States City of Hope National Medical Center Duarte California
United States Masonic Cancer Center, University of Minnesota Minneapolis Minnesota
United States Sarah Cannon Research Institute - Tennessee Oncology Nashville Tennessee
United States Weill Cornell Medical College - New York Presbyterian Hospital New York New York
United States Sarah Cannon Research Institute - Texas Transplant Institute San Antonio Texas
United States University of California at San Diego San Diego California
United States Wake Forest Baptist Health Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Calibr, a division of Scripps Research

Country where clinical trial is conducted

United States, 

References & Publications (2)

Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS, Hardy IR, Schulman A, Du J, Wang F, Singer O, Ma J, Nunez V, Shen J, Woods AK, Wright TM, Schultz PG, Kim CH, Young TS. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68. doi: 10.1073/pnas.1524155113. Epub 2016 Jan 12. — View Citation

Viaud S, Ma JSY, Hardy IR, Hampton EN, Benish B, Sherwood L, Nunez V, Ackerman CJ, Khialeeva E, Weglarz M, Lee SC, Woods AK, Young TS. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. Proc Natl Acad Sci U S A. 2018 Nov 13;115(46):E10898-E10906. doi: 10.1073/pnas.1810060115. Epub 2018 Oct 29. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events 35 days
Primary Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD) up to 1 year
Secondary Maximum drug concentration (Cmax) of SWI019 To determine the maximum concentration of SWI019 in a patient's peripheral blood up to Day 35
Secondary Area under the curve (AUC) of SWI019 To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time up to Day 35
Secondary Time to reach Cmax (Tmax) of SWI019 To identify the time point when the concentration of SWI019 reaches maximum in a patient's peripheral blood up to Day 35
Secondary Clearance (CL) of SWI019 To determine the clearance factor of SWI019 in a patient's peripheral blood up to Day 35
Secondary Apparent elimination half-life (t1/2) of SWI019 To identify the time point when the concentration of SWI019 reaches half of maximum in a patient's peripheral blood up to Day 35
Secondary Quantification of CLBR001 cells in peripheral blood To quantify CLBR001 in a patient's peripheral blood at different time points up to 1 year
Secondary Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies To evaluate the phenotype of CLBR001 in a patient's peripheral blood at different time points by flow cytometry up to 1 year
Secondary Immunogenic response to CLBR001 To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood up to 1 year
Secondary Immunogenic response to SWI019 To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood up to 1 year
Secondary Serum cytokine concentrations 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 up to 1 year
Secondary Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria To determine the overall (best) objective anti-cancer response by RECIL and Lugano criteria up to 1 year
Secondary Duration of response (DOR) To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration up to 1 year
Secondary Progression free survival (PFS) To evaluate the duration of patient's progression-free survival up to 1 year
Secondary Overall survival (OS) To evaluate the overall duration of patient's survival up to 1 year
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