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

August 19, 2024 updated by: Calibr, a division of Scripps Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City Of Hope National Medical Center
      • San Diego, California, United States, 92093
        • University of California at San Diego
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College - New York Presbyterian Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute - Tennessee Oncology
    • Texas
      • San Antonio, Texas, United States, 78229
        • Sarah Cannon Research Institute - Texas Transplant Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
35 days
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)
up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to Day 35
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
up to Day 35
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
up to Day 35
Clearance (CL) of SWI019
Time Frame: up to Day 35
To determine the clearance factor of SWI019 in a patient's peripheral blood
up to Day 35
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
up to Day 35
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
up to 1 year
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
up to 1 year
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
up to 1 year
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
up to 1 year
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
up to 1 year
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
up to 1 year
Duration of response (DOR)
Time Frame: up to 1 year
To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration
up to 1 year
Progression free survival (PFS)
Time Frame: up to 1 year
To evaluate the duration of patient's progression-free survival
up to 1 year
Overall survival (OS)
Time Frame: up to 1 year
To evaluate the overall duration of patient's survival
up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calibr, a division of Scripps Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 14, 2020

Primary Completion (Actual)

May 6, 2024

Study Completion (Actual)

May 6, 2024

Study Registration Dates

First Submitted

June 23, 2020

First Submitted That Met QC Criteria

June 25, 2020

First Posted (Actual)

June 29, 2020

Study Record Updates

Last Update Posted (Actual)

August 20, 2024

Last Update Submitted That Met QC Criteria

August 19, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CBR-sCAR19-3001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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