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

Calibr, a division of Scripps Research

Status and phase: Completed; Phase 1

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

Treatments: Combination Product: CLBR001 and SWI019

Study type: Interventional

Funder types: Other

Identifiers

NCT04450069

CBR-sCAR19-3001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Dose Escalation

Experimental group

Description:

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

Treatment:

Combination Product: CLBR001 and SWI019