This phase I trial tests the safety, side effects, and best dose of loncastuxlmab tesirine with acalabrutinib in treating patients with chronic lymphocytic leukemia (CLL). LoncastuxImab tesirine is a monoclonal antibody called valine-alanine and maleimide, linked to a chemotherapy drug called a pyrrolobenzodiazepine dimer. Valine-alanine and maleimide are forms of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers valine-alanine and maleimide to kill them. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as CLL at abnormal levels. This may help keep cancer cells from growing and spreading. Giving loncastuxlmab tesirine with acalabrutinib may be safe, tolerable and/or effective in treating patients with CLL.
Additional locations may be listed on ClinicalTrials.gov for NCT05971251.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To identify the recommended phase 2 dose (R2PD) of loncastuximab tesirine in combination with acalabrutinib in patients with indolent B-cell lymphomas and chronic lymphocytic leukemia.
SECONDARY OBJECTIVES:
I. To describe the ability of loncastuximab tesirine in attaining undetectable measurable disease (uMRD) at 6 months of combination therapy in peripheral blood by next generation sequencing (NGS) based clonoseq test.
II. To describe the ability of loncastuximab tesirine in attaining undetectable measurable residual disease (uMRD) at 12 months of combination therapy by NGS based clonoseq test.
III. To assess the antitumor activity of loncastuximab tesirine in combination with acalabrutinib.
IV. To measure the ability of loncastuximab tesirine in combination with acalabrutinib in achieving a complete response.
V. To measure the progression free survival (PFS) at 12 months after completion of all treatment.
VI. To determine the safety profile of loncastuximab tesirine in combination with acalabrutinib in CLL.
VII. To determine the duration of response of loncastuximab tesirine in combination with acalabrutinib in CLL.
EXPLORATORY OBJECTIVES:
I. To measure the kinetics and proportion of patients who achieve uMRD as measured by flowcytometry in the peripheral blood at diagnosis, after cycle 3, 6 and 12 of loncastuximab.
II. To measure the proportion of patients who achieve uMRD as measured by flowcytometry in the bone marrow after cycle 12 of loncastuximab.
III. To measure the change of CD19 median fluorescent intensities on flowcytometry with treatment with loncastuximab tesirine.
OUTLINE: This is a dose-escalation study of loncastuxlmab tesirine in combination with acalabrutinib.
Patients receive acalabrutinib orally (PO) twice per day (BID) continuously and loncastuximab tesirine intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. At the end of 12 cycles patients with undetectable measurable residual disease stop therapy and patients positive for measurable residual disease continue on acalabrutinib. Patients undergo blood sample collection throughout the study and bone marrow aspiration during follow up. Patients also undergo computed tomography (CT) on study.
After completion of study treatment, patients are followed up at 30 days and every 12 weeks for 1 year.
Lead OrganizationUniversity of Alabama at Birmingham Cancer Center
Principal InvestigatorMayur Narkhede
