Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Starting soon · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Small Lymphocytic Lymphoma

In brief

This phase II trial tests the safety, side effects and how well giving tafasitamab with acalabrutinib and venetoclax works for the treatment of chronic lymphocytic leukemia (CLL)/small cell lymphoma (SLL). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tafasitamab is a monoclonal antibody that binds to CD19 antigen which is found on the surface of most B cells (a type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. 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 mantle cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab with acalabrutinib and venetoclax may be safe and effective for treating patients with CLL/SLL.

Key facts

Study ID

NCT07582159

Run by

City of Hope Medical Center

People needed

35

Starts

2026-12-19

Expected to finish

2029-04-14

Last updated by the study team

2026-05-12

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
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• 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/SLL, except steroids and/or rituximab to treat autoimmune complications
• Active disease meeting criteria for requiring treatment per the International Workshop on Chronic Lymphocytic Leukemia (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°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) ≥ 500/mm\^3
• Platelets ≥ 30,000/mm\^3
• Total bilirubin ≤ 2 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

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
• Exposure to vaccination with live vaccine within 30 days prior to cycle (C) 1 day (D) 1, 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)
• Active infection
• Known positive test result for hepatitis C (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 active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative hepatitis B surface antigen (HBsAg) and positive hepatitis B core antibody [HBcAb]) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV RNA
• Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 > 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
• 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)

Where it is running

• City of Hope Medical Center — Duarte, California, United States
• City of Hope at Irvine Lennar — Irvine, California, United States

Full record on ClinicalTrials.gov

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