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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 : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Calibr, a division of Scripps Research

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.

Condition or disease Intervention/treatment Phase
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 Combination Product: CLBR001 and SWI019 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 14, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : April 2024


Arm Intervention/treatment
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)
Combination Product: CLBR001 and SWI019
Investigational immunotherapy for B cell malignancies




Primary Outcome Measures :
  1. 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

  2. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Clearance (CL) of SWI019 [ Time Frame: up to Day 35 ]
    To determine the clearance factor of SWI019 in a patient's peripheral blood

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Duration of response (DOR) [ Time Frame: up to 1 year ]
    To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration

  13. Progression free survival (PFS) [ Time Frame: up to 1 year ]
    To evaluate the duration of patient's progression-free survival

  14. Overall survival (OS) [ Time Frame: up to 1 year ]
    To evaluate the overall duration of patient's survival



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04450069


Contacts
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Contact: Pamela Garzone, Ph.D. 858-242-1072 pgarzone@scripps.edu

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Liana Nikolaenko    833-310-2278      
Principal Investigator: Liana Nikolaenko, MD         
University of California at San Diego Recruiting
San Diego, California, United States, 92093
Contact: Jesika Reiner    858-822-5364    jreiner@health.ucsd.edu   
Contact: Ben Brookhart    858-822-3614    bbrookhart@health.ucsd.edu   
Principal Investigator: Carolyn Mulroney, MD         
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Peter Riedell    773-702-1994    BMT.Intake@uchospitals.edu   
Contact: Michael Gomez    773-702-1994    Mgomez9@medicine.bsd.uchicago.edu   
Principal Investigator: Peter Riedell, MD         
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Matthew Price    615-636-2449    matthew.price@sarahcannon.com   
Contact: Jared McAlister    615-636-6338    Jared.McAlister@sarahcannon.com   
Principal Investigator: Ian Flinn, MD, PhD         
United States, Texas
Sarah Cannon Research Institute - Texas Transplant Institute Recruiting
San Antonio, Texas, United States, 78229
Contact: Sherri Shade    210-575-4238    sherri.shade@mhshealth.com   
Contact: Antony Opwora    210-575-3096    aso.opwora@mhshealth.com   
Principal Investigator: Cesar Freytes, MD         
Sponsors and Collaborators
Calibr, a division of Scripps Research
Investigators
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Principal Investigator: Carolyn Mulroney, MD University of California, San Diego
Publications:
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Responsible Party: Calibr, a division of Scripps Research
ClinicalTrials.gov Identifier: NCT04450069    
Other Study ID Numbers: CBR-sCAR19-3001
First Posted: June 29, 2020    Key Record Dates
Last Update Posted: September 11, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calibr, a division of Scripps Research:
CAR-T Cell Therapy
Switchable CAR-T Cell
Autologous Cell Therapy
CD19 Positive Disease
CD19 CAR-T Cell
Blood Cancer
Hematological malignancy
Neoplasms
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell