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

NCT ID: NCT04450069

Last Updated: 2024-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-14

Study Completion Date

2024-05-06

Brief Summary

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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

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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.

Conditions

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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 Waldenstrom Macroglobulinemia Lymphoplasmacytic Lymphoma Burkitt Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation

CLBR001 + SWI019 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD)

Group Type EXPERIMENTAL

CLBR001 and SWI019

Intervention Type COMBINATION_PRODUCT

Investigational immunotherapy for B cell malignancies

Interventions

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CLBR001 and SWI019

Investigational immunotherapy for B cell malignancies

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Calibr, a division of Scripps Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California at San Diego

San Diego, California, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Sarah Cannon Research Institute - Texas Transplant Institute

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26759369 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30373813 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34515338 (View on PubMed)

Other Identifiers

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CBR-sCAR19-3001

Identifier Type: -

Identifier Source: org_study_id

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