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Relapsed/Refractory B-cell LymphomasPhase 1NCT04450069

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

A Phase 1 study testing CLBR001 and SWI019 in people with Relapsed/Refractory B-cell Lymphomas and Diffuse Large B Cell Lymphoma (DLBCL), run by Calibr, a division of Scripps Research at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CLBR001 and SWI019
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
8 sitesUnited States
Study dates
14 Aug 2020to 6 May 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Chicago

    Chicago, Illinois, 60637

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Sarah Cannon Research Institute - Tennessee Oncology

    Nashville, Tennessee, 37203

  • Weill Cornell Medical College - New York Presbyterian Hospital

    New York, New York, 10065

  • Sarah Cannon Research Institute - Texas Transplant Institute

    San Antonio, Texas, 78229

  • University of California at San Diego

    San Diego, California, 92093

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
CLBR001 and SWI019
Keywords
CAR-T Cell Therapy, Switchable CAR-T Cell, Autologous Cell Therapy, CD19 Positive Disease, CD19 CAR-T Cell, Blood Cancer, Hematological malignancy, Neoplasms
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLBR001 and SWI019Combination product

    Investigational immunotherapy for B cell malignancies

Study groups in NCT04450069
Study groupRoleWhat they receive
Dose EscalationExperimentalCLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)
Receives: Combination Product: CLBR001 and SWI019

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 35 days

  2. 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)

    Measured: up to 1 year

Secondary outcomes (14)

  1. Maximum drug concentration (Cmax) of SWI019

    To determine the maximum concentration of SWI019 in a patient's peripheral blood

    Measured: up to Day 35

  2. Area under the curve (AUC) of SWI019

    To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time

    Measured: up to Day 35

  3. 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

    Measured: up to Day 35

  4. Clearance (CL) of SWI019

    To determine the clearance factor of SWI019 in a patient's peripheral blood

    Measured: up to Day 35

  5. 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

    Measured: up to Day 35

  6. Quantification of CLBR001 cells in peripheral blood

    To quantify CLBR001 in a patient's peripheral blood at different time points

    Measured: up to 1 year

  7. 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

    Measured: up to 1 year

  8. Immunogenic response to CLBR001

    To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood

    Measured: up to 1 year

  9. Immunogenic response to SWI019

    To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood

    Measured: up to 1 year

  10. 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

    Measured: up to 1 year

  11. 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

    Measured: up to 1 year

  12. Duration of response (DOR)

    To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration

    Measured: up to 1 year

  13. Progression free survival (PFS)

    To evaluate the duration of patient's progression-free survival

    Measured: up to 1 year

  14. Overall survival (OS)

    To evaluate the overall duration of patient's survival

    Measured: up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2020
  2. Study start14 Aug 2020
  3. Primary completion6 May 2024
  4. Study completion6 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04450069
Sponsor's protocol ID
CBR-sCAR19-3001
Status last verified
Aug 2024
First submitted
23 Jun 2020
Last updated
20 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26759369

  • 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.

    PubMed 30373813

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PubMed 34515338

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CLBR001 and SWI019 in people with Relapsed/Refractory B-cell Lymphomas and Diffuse Large B Cell Lymphoma (DLBCL), run by Calibr, a division of Scripps Research at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events (time frame: 35 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04450069, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2024.

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