Tafasitamab and Zanubrutinib for the Treatment of Patients With Newly Diagnosed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, TaZA CLL Study

Running, not enrolling · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

In brief

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.

Key facts

Study ID

NCT05718869

Run by

City of Hope Medical Center

People needed

26

Starts

2023-05-18

Expected to finish

2026-09-08

Last updated by the study team

2026-05-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• 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:
• Unintentional weight loss > 10% within the previous 6 months prior to screening
• Extreme fatigue (unable to work or perform usual activities)
• Fevers of greater than 100.5 degrees Fahrenheit (F) for >= 2 weeks without evidence of infection
• Night sweats without evidence of infection
• 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
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease 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

You may not qualify if…

• 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.
• For patients intended to enroll on dose level (DL) -1 use of strong CYP3A inhibitors will be prohibited on-therapy and their use must be stopped at minimum 2 weeks prior to the first day of study therapy
• 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:
• Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study
• Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
• Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease
• Asymptomatic prostate cancer managed with "watch and wait" strategy
• 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)
• Participants with occult or prior HBV infection (defined as negative HBsAg and positive total hepatitis B core antibody) may be included if HBV deoxyribonucleic acid (DNA) was undetectable, provided that they are willing to undergo ongoing DNA testing.
• Antiviral prophylaxis may be administered as per institutional guidelines.
• Participants who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible
• Known seropositive for or history of active viral infection with human immunodeficiency virus (HIV)
• Clinically significant cardiovascular disease including the following:
• Myocardial infarction within 6 months before screening
• Unstable angina within 3 months before screening
• New York Heart Association class III or IV congestive heart failure
• History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes)
• QTcF > 480 milliseconds based on Fridericia's formula

Where it is running

• City of Hope Medical Center — Duarte, California, United States
• City of Hope at Irvine Lennar — Irvine, California, United States
• University of Miami Sylvester Comprehensive Cancer Center — Miami, Florida, United States

Full record on ClinicalTrials.gov

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