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

NCT07582159 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 25409NCI-2026-03205P30CA033572
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of unacceptable toxicity

  Defined as toxicities deemed related (possibly, probably or definitely) to the study drugs.

  From cycle 1 day 1 to completion of cycle 4 (cycle length = 28 days)

• Complete response with undetectable minimal residual disease (MRD)

  Complete response is defined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria; undetectable is defined as \< 10\^-4 CLL cells in the peripheral blood by flow cytometry. Will be estimated by the proportion of evaluable patients achieving that endpoint, along with the 95% exact binomial confidence interval.

  At the end of therapy after a minimum of 4 cycles

Secondary Outcomes (5)

• Overall response

  Up to 3 years

• Progression free survival

  From start of protocol treatment to disease relapse/progression or death due to any cause, up to 3 years

• Duration of response

  From the first achievement of CR or PR on this study to disease progression/relapse or death due to any cause, up to 3 years

• Overall survival

  From the start of protocol treatment to death due to any cause, up to 3 years

• Incidence of adverse events

  Up to 3 years

Study Arms (1)

Treatment (Tafasitamab, acalabrutinib, venetoclax)

EXPERIMENTAL

See Detailed Description

Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Biological: Tafasitamab; Drug: Venetoclax

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP 196, ACP-196, ACP196, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Tafasitamab BIOLOGICAL

Given IV

Also known as: Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer, Monjuvi, MOR 00208, MOR 208, MOR-00208, MOR-208, MOR00208, MOR208, Tafasitamab-cxix, XmAb-5574, XmAb5574

Treatment (Tafasitamab, acalabrutinib, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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;
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; Specimen Handling; Biopsy; Magnetic Resonance Spectroscopy; tafasitamab; Immunoglobulins; Disulfides; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Benjamin M Heyman

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 12, 2026
• Study Start (Estimated): December 19, 2026
• Primary Completion (Estimated): April 14, 2029
• Study Completion (Estimated): April 14, 2029
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

US (2)