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

NCT05718869 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 22183NCI-2022-10205P30CA033572
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete response (CR) rate

  Defined as the proportion of response evaluable patients who achieve a complete response according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 guidelines on study before any documented disease progression or any subsequent chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment. CR rate will be estimated by the proportion of response-evaluable patients achieving CR, along with the 95% exact binomial confidence interval.

  Up to 5 years

• Incidence of adverse events

  Grading of toxicities will be according to National Cancer Institute's Common Terminology Criteria for Adverse Events version 5. Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity, and attribution.

  Up to 5 years

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 5 years

• Progression-free survival (PFS)

  From start of protocol treatment to disease relapse/progression or death due to any cause, assessed up to 5 years

• Duration of response (DOR)

  From the first achievement of CR or PR to disease progression/relapse or death due to any cause, assessed up to 5 years

• Undetectable minimal residual disease (uMRD) rate

  On day 1 of cycles 1, 4, 7, 13, 18, and 24 ( each cycle is 28 days)

Study Arms (1)

Treatment (tafasitamab and zanubrutinib)

EXPERIMENTAL

Patients receive tafasitamab IV and zanubrutinib PO on study. Patients also undergo collection of blood samples on study and undergo CT scan and bone marrow biopsy throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Tafasitamab; Drug: Zanubrutinib

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (tafasitamab and zanubrutinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (tafasitamab and zanubrutinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (tafasitamab and zanubrutinib)

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, MOR00208, MOR208, Tafasitamab-cxix, XmAb5574

Treatment (tafasitamab and zanubrutinib)

Zanubrutinib DRUG

Given PO

Also known as: BGB-3111, Brukinsa, BTK-InhB

Treatment (tafasitamab and zanubrutinib)

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
• 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

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
• 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.

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33146, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Specimen Handling; Biopsy; tafasitamab; Immunoglobulins; Disulfides; zanubrutinib

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; 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

• Matthew Mei

  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: January 20, 2023
• First Posted: February 8, 2023
• Study Start: May 18, 2023
• Primary Completion: April 19, 2026
• Study Completion: April 19, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-11

Locations

US (3)