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

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04450069
• Other study ID #: CBR-sCAR19-3001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 14, 2020
• Est. completion date: June 2024

Study information

• Verified date: January 2024
• Source: Calibr, a division of Scripps Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: June 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Chronic Lymphocytic Leukemia (CLL)
• Diffuse Large B Cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoplasmacytic Lymphoma
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma (MZL)
• Neoplasms
• Primary Mediastinal Large B Cell Lymphoma
• Relapsed/Refractory B-cell Lymphomas
• Small Lymphocytic Lymphoma (SLL)
• Transformed Follicular Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Combination Product:
• CLBR001 and SWI019
Investigational immunotherapy for B cell malignancies

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	City of Hope National Medical Center	Duarte	California
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Sarah Cannon Research Institute - Texas Transplant Institute	San Antonio	Texas
United States	University of California at San Diego	San Diego	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Calibr, a division of Scripps Research

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Maximum drug concentration (Cmax) of SWI019	To determine the maximum concentration of SWI019 in a patient's peripheral blood	up to Day 35
Secondary	Area under the curve (AUC) of SWI019	To quantify the cumulative amount of SWI019 in a patient's peripheral blood over time	up to Day 35
Secondary	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	up to Day 35
Secondary	Clearance (CL) of SWI019	To determine the clearance factor of SWI019 in a patient's peripheral blood	up to Day 35
Secondary	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	up to Day 35
Secondary	Quantification of CLBR001 cells in peripheral blood	To quantify CLBR001 in a patient's peripheral blood at different time points	up to 1 year
Secondary	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	up to 1 year
Secondary	Immunogenic response to CLBR001	To evaluate the anti-drug antibodies in response to CLBR001 administration in a patient's peripheral blood	up to 1 year
Secondary	Immunogenic response to SWI019	To evaluate the anti-drug antibodies in response to SWI019 administration in a patient's peripheral blood	up to 1 year
Secondary	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	up to 1 year
Secondary	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	up to 1 year
Secondary	Duration of response (DOR)	To evaluate the duration of anti-cancer response after CLBR001 and SWI019 administration	up to 1 year
Secondary	Progression free survival (PFS)	To evaluate the duration of patient's progression-free survival	up to 1 year
Secondary	Overall survival (OS)	To evaluate the overall duration of patient's survival	up to 1 year