Tafasitamab, Acalabrutinib, and Obinutuzumab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

NCT05943496 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: STUDY00024507NCI-2023-04657
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety and effectiveness of tafasitamab, acalabrutinib, and obinutuzumab in treating patients with previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). CLL and SLL are types of cancer that develops from a specific white blood cell called B cells or B lymphocytes. Tafasitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell cancers such as CLL at abnormal levels. This may help keep cancer cells from growing and spreading. Giving tafasitamab, acalabrutinib, and obinutuzumab may kill more cancer cells in patients with previously untreated CLL and SLL.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs)

  Incidences of DLTs, serious AEs, and AEs of special interest experienced during cycle 2-6 evaluated. The severity of the AE assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The international working chronic lymphocytic leukemia (iwCLL) grading system for hematological toxicities also utilized. Incidence and type of DLT reported.

  From first dose of tafasitamab (cycle 2, day 1) to end of cycle 6 (C6D28) up to 2 years. (cycle length = 28 days)

• Proportion of patients that achieve minimal residual disease (MRD) negativity in peripheral blood

  MRD negativity in patients reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval (CI) reported.

  From first dose of study drug (cycle 1, day 1) to 3, 6, 9, 12 months and 1-3 months after last dose of acalabrutinib up to 2 years.(cycle length = 28 days)

Secondary Outcomes (1)

• Objective response rate (ORR)

  From cycle 1, day 1 to any complete response (CR) or partial response (PR) through cycle 12 up to 2 years.(cycle length = 28 days)

Study Arms (1)

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

EXPERIMENTAL

See Detailed DescriptionPatients receive obinutuzumab IV over a rate titrated up to 400 mg/hour on days 1, 2, 8, and 15 for cycle 1 then on day 1 for cycles 2-6 and tafasitamab IV over 1.5-2 hours on days 1, 4, 8, 15, and 22 for cycle 2, on days 1, 8, 15, and 22 for cycles 3-4, and on days 1 and 15 for cycles 5-7. Patients also receive acalabrutinib PO BID in each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT throughout the trial. Patients may undergo an ECHO at baseline as clinically indicated and may also undergo bone marrow biopsy and/or aspiration at baseline and/or follow-up.

Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: Obinutuzumab; Other: Questionnaire Administration; Biological: Tafasitamab

Interventions

Acalabrutinib DRUG

Given PO

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

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and/or aspiration

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and/or aspiration

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

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Computed Tomography PROCEDURE

Undergo CT scan

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

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (tafasitamab, obinutuzumab, acalabrutinib)

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, obinutuzumab, acalabrutinib)

Eligibility Criteria

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

You may qualify if:

• Written informed consent. Participant or legally authorized representative (LAR) must provide written informed consent prior to any study-specific procedures or interventions
• Age \>= 18 years. All genders, races, and ethnic groups will be included
• Ability to swallow and retain oral medication
• Documented previously untreated CLL/SLL. Diagnosis must be confirmed by peripheral blood flow cytometry or lymph node biopsy and made in accordance with international workshop (iw)CLL diagnostic criteria
• Baseline detectable immunoglobulin heavy (IGH) gene signature determined as part of clonoSEQ for minimal residual disease (MRD) testing
• Must meet at least 1 criterion for treatment based on iwCLL guidelines
• Evidence of progressive marrow failure as manifested by the onset or worsening of anemia and/or thrombocytopenia, or
• Massive (i.e., lower edge of spleen \>= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
• Massive (i.e., \>= 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
• Progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (ALC) \> 50% over a 2 month period, or lymphocyte doubling time of \< 6 months (as long as initial ALC was \>= 30,000/uL), or
• Autoimmune anemia and / or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or
• Constitutional symptoms, defined as any one or more of the following disease related symptoms or signs occurring in the absence of evidence of infection:
• Unintentional weight loss of \>= 10% within the previous 6 months, or
• Significant fatigue (grade \>= 2), or
• Fevers \> 100.5°F or 38.0°C for \>= 2 weeks, or

You may not qualify if:

• Previous or concurrent diagnosis of any other hematologic malignancy
• Any previous CLL-directed treatment. Use of corticosteroids (or ongoing prednisone =\< 20 mg daily, or equivalent) for symptom control are permitted. Enrollment will be considered for those individuals that can taper ongoing use of a corticosteroid at \> 20 mg daily to 0 mg within 14 days after C1D1
• Known history of hypersensitivity to
• Humanized or murine monoclonal antibodies or products
• A CD19 or CD20 antibody
• Tafasitamab
• Acalabrutinib
• Receipt of live vaccine within 14 days of trial enrollment
• Prior history of any solid malignancy, unless disease-free for over 2 years, exclusive of any prior history of squamous cell carcinoma of the skin or cervix, basal cell carcinoma of the skin, transitional cell urothelial carcinoma, prostate cancer, or early-stage melanoma. Exceptions will be considered, at the discretion of the investigator, if the prior treatment (i.e., within 2 years) is not expected to confound the results of this study
• Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
• Active autoimmune disease requiring treatment with \> 20 mg of prednisone (or prednisone equivalent daily), apart from autoimmune hemolytic anemia or immune thrombocytopenic purpura (ITP).
• Evidence of ongoing systemic bacterial, fungal, or viral infection, except localized fungal infections of skin or nails. NOTE: Participants may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator
• Seropositivity for, or history of active viral infection with, human immunodeficiency virus (HIV)
• Known histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)
• Known bleeding disorders

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Incyte Corporation: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; Specimen Handling; Biopsy; obinutuzumab; tafasitamab; Immunoglobulins; Disulfides

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

• Stephen E Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: October 2, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (1)