Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This phase II trial tests how well tafasitamab and zanubrutinib works in treating patients with newly diagnosed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Zanubrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein that signals cancer cells to multiply. This may stop the growth and spread of cancer cells. Giving tafasitamab and zanubrutinib in combination may kill more cancer cells in patients with CLL/SLL than giving either treatment alone.
Full description
PRIMARY OBJECTIVES:
I. To evaluate the safety/tolerability of tafasitamab and zanubrutinib (as assessed by unacceptable toxicity) in patients with newly diagnosed CLL. (Safety lead-in) II. To evaluate the anti-tumor activity of tafasitamab and zanubrutinib as assessed by complete response (CR) rate per International Workshop on CLL (iwCLL) 2018 criteria in patients with newly diagnosed CLL. (Phase 2)
SECONDARY OBJECTIVES:
I. To assess the toxicity of the combination of tafasitamab and zanubrutinib through evaluation of toxicities.
II. To obtain estimates of overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR).
III. To assess the undetectable minimal residual disease (uMRD) rate in response to tafasitamab and zanubrutinib.
EXPLORATORY OBJECTIVES:
I. To assess the effect of tafasitamab and zanubrutinib combination on immune function of T cells and NK cells.
II. To explore mechanisms of resistance to the combination of tafasitamab and zanubrutinib.
III. To investigate the association of established biomarkers (chromosomal abnormalities, immunoglobulin heavy chain [IGHV] mutational status, TP53 mutational status) with response (ORR and PFS) to tafasitamab and zanubrutinib in patients with CLL.
OUTLINE: This is a dose-escalation study of zanubrutinib followed by a phase II study.
Patients receive tafasitamab intravenously (IV) and zanubrutinib orally (PO) on study. Patients also collection of blood samples on study and undergo computed tomography (CT) scan and bone marrow biopsy throughout the trial.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Documented informed consent of the participant and/or legally authorized representative
Age: >= 18 years
Eastern Cooperative Oncology Group (ECOG) =< 2
Histologically or flow cytometry confirmed diagnosis of B-CLL/SLL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO)
No prior treatment for CLL, except steroids and/or rituximab to treat autoimmune complications
Active disease meeting criteria for requiring treatment per the iwCLL 2018 guidelines
A minimum of any one of the following constitutional symptoms:
Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia
Massive (i.e., > 6 cm below the left costal margin), progressive or symptomatic splenomegaly
Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive lymphadenopathy
Progressive lymphocytosis with an increase of > 50% over a 2-month period, or an anticipated doubling time of less than 6 months
Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids
Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine)
Participant must be able to swallow tablets or capsules. A participant with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible
Absolute neutrophil count (ANC) >= 1,000/mm^3 unless due to bone marrow involvement
Platelets >= 75,000/mm^3 unless due to bone marrow involvement, and independent of transfusion support, with no active bleeding
Direct bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or compensated hemolysis directly attributable to CLL)
Aspartate aminotransferase (AST) =< 2.5 X ULN
Alanine aminotransferase (ALT) =< 2.5 X ULN
Estimated creatinine clearance of >= 30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
IF NOT RECEIVING ANTICOAGULANTS: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN; IF ON ANTICOAGULANT THERAPY: PT must be within therapeutic range of intended use of anticoagulants
IF NOT RECEIVING ANTICOAGULANTS: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN; IF ON ANTICOAGULANT THERAPY: aPTT must be within therapeutic range of intended use of anticoagulants
Women of childbearing potential (WOCBP): negative serum pregnancy test
Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Contraception methods include the following:
Exclusion criteria
Chronic use of corticosteroids in excess of 20 mg/day prednisone or its equivalent
Major surgery (under general anesthesia) within 30 days prior to therapy
Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are allowed
Use of moderate or strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks of the first day of study therapy. CYP3A inhibitors are allowed.
Exposure to vaccination with live vaccine within 30 days prior to cycle 1 day 1 (C1D1), or anticipated need for such vaccination during treatment
History of prior malignancy except:
Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)
Known positive test result for SARS-CoV-2 unless follow-up test was negative or investigator deems the infection is fully resolved
Known positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing) and a positive test result for HCV ribonucleic acid (RNA). Participants with positive serology are eligible in case of negative HCV RNA test results
Known positive test result for chronic hepatitis B virus (HBV) infection (defined by hepatitis B virus surface antigen [HBsAg] positivity)
Known seropositive for or history of active viral infection with human immunodeficiency virus (HIV)
Clinically significant cardiovascular disease including the following:
Known severe chronic obstructive pulmonary disease (COPD)
Known hepatic cirrhosis or severe pre-existing hepatic impairment
Major surgery (requiring general anesthesia) within 14 days before the first dose of study drug or a scheduled surgery during study period
Patients with clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting or any other condition that will interfere significantly with drug absorption
Females only: Pregnant or breastfeeding
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Primary purpose
Allocation
Interventional model
Masking
25 participants in 1 patient group
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal