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

NCT04450069 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CBR-sCAR19-3001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Keywords

CAR-T Cell Therapy; Switchable CAR-T Cell; Autologous Cell Therapy; CD19 Positive Disease; CD19 CAR-T Cell; Blood Cancer; Hematological malignancy; Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (14)

• Maximum drug concentration (Cmax) of SWI019

  up to Day 35

• Area under the curve (AUC) of SWI019

  up to Day 35

• Time to reach Cmax (Tmax) of SWI019

  up to Day 35

• Clearance (CL) of SWI019

  up to Day 35

• Apparent elimination half-life (t1/2) of SWI019

  up to Day 35

Study Arms (1)

Dose Escalation

EXPERIMENTAL

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

Interventions

CLBR001 and SWI019 COMBINATION_PRODUCT

Investigational immunotherapy for B cell malignancies

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Calibr, a division of Scripps Research: lead

Study Sites (8)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California at San Diego

San Diego, California, 92093, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Weill Cornell Medical College - New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Sarah Cannon Research Institute - Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Related Publications (3)

• 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.

  PMID: 26759369 BACKGROUND

• 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.

  PMID: 30373813 BACKGROUND

• 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.

  PMID: 34515338 DERIVED

MeSH Terms

Conditions

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; Hematologic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 29, 2020
• Study Start: August 14, 2020
• Primary Completion: May 6, 2024
• Study Completion: May 6, 2024
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)