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Chronic Lymphocytic LeukemiaPhase 2NCT07582159

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

A Phase 2 study testing Acalabrutinib, Biospecimen Collection and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib, Biospecimen Collection and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
19 Dec 2026to 14 Apr 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Alanine aminotransferase ≤ 2.5 x ULN
  • Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
  • If not receiving anticoagulants: International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • If not receiving anticoagulants: Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  • If seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on active anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study and after completion of study treatment as described below separately for males and females.
  • Female participants must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 2 days after the final dose of acalabrutinib, 30 days after the last dose of venetoclax, and 3 months after the final dose of tafasitamab, whichever is longer. Women must refrain from donating eggs during this same period.
  • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
  • Hormonal contraceptive methods must be supplemented by a barrier method.
  • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm, as defined below:
  • With a female partner of childbearing potential or pregnant female partners, male participants must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 2 days after the final dose of acalabrutinib, 90 days after the last dose of venetoclax, and 3 months after the final dose of tafasitamab, whichever is longer. Male participants must refrain from donating sperm during this same period.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
  • A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Contraception methods include the following:
  • Combined (estrogen- and progestogen- containing) hormonal contraception associated with the inhibition of ovulation
  • Oral, intravaginal, or transdermal
  • Progestogen-only hormonal contraception associated with the inhibition of ovulation
  • Oral, injectable, implantable
  • An intrauterine device
  • Intrauterine hormone-releasing system
  • Bilateral tubal occlusion Vasectomized partner (provided that the vasectomized partner is the sole sexual partner of the woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of surgical success)
  • Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib or ibrutinib. Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception, and, if used, this method must be used in combination with another acceptable method listed above. If patient is using hormonal contraceptives such as birth control pills or devices, a barrier method of contraception (eg, condoms) must also be used. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle-stimulating hormone measurement is insufficient

Who cannot join

  • 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:
Show all 18Show fewer
  • 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)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites, 2 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Benjamin M. Heyman, 626-218-2405, bheyman@coh.org

    Benjamin M. Heyman

    Recruiting

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Benjamin M. Heyman, 626-218-2405, bheyman@coh.org

    Benjamin M. Heyman

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of Acalabrutinib, Venetoclax and Tafasitamab (AVT) in Patients With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of tafasitamab in combination with acalabrutinib and venetoclax, as assessed by unacceptable toxicity, in patients with previously untreated CLL/SLL. (Safety lead-in) II. To evaluate efficacy of tafasitamab in combination with acalabrutinib and venetoclax, as assessed by complete response (CR) with undetectable minimal residual disease (MRD) by flow cytometry in peripheral blood, in patients with previously untreated CLL/SLL. (Phase 2)

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of tafasitamab in combination with acalabrutinib and venetoclax, as assessed by all toxicities.

II. To evaluate efficacy of tafasitamab in combination with acalabrutinib and venetoclax, as assessed by overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. To evaluate MRD status in the bone marrow by flow cytometry and by Clonoseq in patients with previously untreated CLL/SLL treated with tafasitamab in combination with acalabrutinib and venetoclax.

II. To explore the association between the potential risk factors (including IGHV mutation, del17p/TP53 mutation, complex cytogenetics) and the clinical outcomes in patients with previously untreated CLL/SLL treated with tafasitamab in combination with acalabrutinib and venetoclax.

OUTLINE:

CYCLES 1 AND 2: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CYCLES 3-5: Patients receive acalabrutinib PO BID, venetoclax PO once daily (QD) on days 1-28, and tafasitamab intravenously (IV) over 1.5-2.5 hours on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CYCLES 6-8: Patients receive acalabrutinib PO BID, venetoclax PO QD on days 1-28, and tafasitamab IV over 1.5-2.5 hours on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

CYCLES 9-14: Patients receive acalabrutinib PO BID and venetoclax PO QD on days 1-28 and tafasitamab IV over 1.5-2.5 hours on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo urine sample collection and bone marrow biopsy at screening, as well as computed tomography (CT) scan or positron emission tomography (PET)-CT scan and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months until progressive disease, then every 6 months, up to 3 years.

Being tested
Acalabrutinib, Biospecimen Collection, Bone Marrow Biopsy, Computed Tomography, Positron Emission Tomography
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called ACP 196, ACP-196, ACP196, Bruton Tyrosine Kinase Inhibitor ACP-196

    Given PO

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

  • TafasitamabBiological

    Also called 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

    Given IV

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

Study groups in NCT07582159
Study groupRoleWhat they receive
Treatment (Tafasitamab, acalabrutinib, venetoclax)ExperimentalSee Detailed Description
Receives: Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Biological: Tafasitamab; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of unacceptable toxicity

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

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

  2. 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.

    Measured: At the end of therapy after a minimum of 4 cycles

Secondary outcomes (5)

  1. Overall response

    Defined as achieving complete response (CR) or partial response (PR) according to iwCLL 2018 guidelines on this study before any documented disease progression or any subsequent treatment. Will be estimated by the proportion of evaluable patients achieving that endpoint, along with the 95% exact binomial confidence interval.

    Measured: Up to 3 years

  2. Progression free survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the PFS estimate at specific timepoint will be constructed based on log-log transformation. Median PFS will be estimated when available.

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

  3. Duration of response

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the DOR estimate at specific timepoint will be constructed based on log-log transformation. Median DOR will be estimated when available.

    Measured: 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

  4. Overall survival

    Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the OS estimate at specific timepoint will be constructed based on log-log transformation. Median OS will be estimated when available.

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

  5. Incidence of adverse events

    Grading of platelet, hemoglobin, and neutrophils toxicities will be conducted according to iwCLL 2018 criteria. Grading of all other toxicities will be according to National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2026
  2. Study start19 Dec 2026 (estimated)
  3. Primary completion14 Apr 2029 (estimated)
  4. Study completion14 Apr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07582159
Sponsor's protocol ID
25409
Other IDs
NCI-2026-03205, 25409, P30CA033572
Status last verified
Nov 2026
First submitted
6 May 2026
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib, Biospecimen Collection and Bone Marrow Biopsy in people with Chronic Lymphocytic Leukemia and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by City of Hope Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 47 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of unacceptable toxicity (time frame: From cycle 1 day 1 to completion of cycle 4 (cycle length = 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07582159.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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