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B-Cell Non-Hodgkin LymphomaPhase 1/2NCT04257578

Acalabrutinib and Anti-CD19 CAR T-cell Therapy for the Treatment of B-cell Lymphoma

A Phase 1/2 study testing Acalabrutinib and Axicabtagene Ciloleucel in people with B-Cell Non-Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by University of Washington at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I/II trial studies the safety of acalabrutinib and axicabtagene ciloleucel in treating patients with B-cell lymphoma. Acalabrutinib may stop the growth of tumor cells by blocking key pathways needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib and Axicabtagene Ciloleucel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
2 Dec 2020to 1 Mar 2031
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, and indolent (grade 1-3a) FL
  • Criteria must be met for receiving commercial axi-cel per Food and Drug Administration (FDA) label
  • >= 18 years of age
  • Patients must be capable of understanding and providing a written informed consent
  • Negative serum pregnancy test within 2 days of initiating acalabrutinib for women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
  • Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods before, during, and for at least 4 months after the CAR T-cell infusion or within 2 days of acalabrutinib, whichever is longer
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Creatine clearance (CrCl) > 50 mL/min or serum creatinine =< 2.5
  • Total bilirubin =< 1.5x the upper limit of normal
  • Adequate pulmonary function, defined as =< grade 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3x the upper limit of normal
  • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of >= 50% and without evidence for pericardial effusion
  • At least 1 measurable lesion >= 15 mm according to the International Working Group consensus response evaluation criteria in lymphoma (Younes 2017)
  • HIV POSITIVE COHORT: Human immunodeficiency virus (HIV)-1 or HIV-2 infection, as documented by any federally approved, licensed HIV test
  • HIV POSITIVE COHORT: HIV plasma HIV-1 ribonucleic acid (RNA) below detected limit obtained by Food and Drug Administration (FDA)-approved assays within 4 weeks prior to registration
  • HIV POSITIVE COHORT: CD4 cell count greater than 200 cells/mm3 obtained within 2 weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent
  • HIV POSITIVE COHORT: Anti-retroviral treatment (ART) should be initiated > 4 weeks prior to study drug so that toxicity assessment of ART is separated from study drug. If patient is on an ART regimen that contains a strong CYP3A inhibitor (e.g ritonavir and cobicistat) or CYP3A inducer (e.g. efavirenz), changes in ART therapy should be considered in collaboration with HIV provider
  • HIV POSITIVE COHORT: No acute active HIV-associated opportunistic infection requiring antibiotic treatment
  • HIV POSITIVE COHORT: No uncontrolled systemic fungal, bacterial, viral, or other infection
  • HIV POSITIVE COHORT: Hemoglobin > 8.0 g/dl
  • HIV POSITIVE COHORT: Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min AST and ALT < 2.5 x ULN

Who cannot join

  • Active and uncontrolled systemic or clinically significant infection that would contraindicate myelosuppressive therapy or CART infusion
  • Patients intolerant of acalabrutinib
  • Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
  • Patients with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases
  • History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
  • Use of a strong CYP3A inhibitor OR inducer within 7 days of starting study drugs or requirement of use of strong CYP3A inhibitor OR inducer at the time of enrollment
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  • Disease that is known to be refractory to BTK inhibition
  • Absolute neutrophil count (ANC) < 1000/ul
  • Platelets < 50K/ul
  • Another active malignancy requiring systemic treatment, unless approved by principal investigator (PI)
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
  • Inability to swallow whole pills, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass
  • Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
  • Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
  • Receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug
  • Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of Lupus anticoagulant) > 2 x upper limit of normal (ULN)
  • History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
  • Major surgical procedure within 7 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
  • Pregnant or breast feeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Acalabrutinib in Combination With Anti-CD19 Chimeric Antigen Receptor T-Cells (CART) in B-Cell Lymphoma

This phase I/II trial studies the safety of acalabrutinib and axicabtagene ciloleucel in treating patients with B-cell lymphoma. Acalabrutinib may stop the growth of tumor cells by blocking key pathways needed for cell growth. Immunotherapy with axicabtagene ciloleucel is engineered to target a specific surface antigen on lymphoma cells. Acalabrutinib may enhance the efficacy of axicabtagene ciloleucel in treating patients with B-cell lymphoma.

Read the detailed description

OUTLINE:

Beginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib orally (PO) every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel intravenously (IV) at 36-96 hours after completion of lymphodepleting chemotherapy.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Being tested
Acalabrutinib, Axicabtagene Ciloleucel
Keywords
Non-Hodgkin Lymphoma
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Non-Hodgkin

What participants receive

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

  • AcalabrutinibDrug

    Also called 1420477-60-6, ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196

    Given PO

  • Axicabtagene CiloleucelBiological

    Also called KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

    Given IV

Study groups in NCT04257578
Study groupRoleWhat they receive
Treatment (acalabrutinib, axicabtagene ciloleucel) - HIV-negative CohortExperimentalBeginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib PO every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel IV at 36-96 hours after completion of lymphodepleting chemotherapy.
Receives: Drug: Acalabrutinib; Biological: Axicabtagene Ciloleucel
Treatment (acalabrutinib, axicabtagene ciloleucel) - HIV-positive CohortExperimentalBeginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib PO every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel IV at 36-96 hours after completion of lymphodepleting chemotherapy.
Receives: Drug: Acalabrutinib; Biological: Axicabtagene Ciloleucel

What is being measured

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

  1. Incidence of Adverse Events

    Toxicity as defined by the following: grade >= 3 cytokine release syndrome, grade >= 3 neurotoxicity within 30 days of infusion of axicabtagene ciloleucel. Grading will be done in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for neurotoxicity and the Lee Criteria for cytokine release syndrome, unless otherwise specified.

    Measured: Up to 30 days post axicabtagene ciloleucel infusion

Secondary outcomes (4)

  1. Complete Response Rate Following Chimeric Antigen Receptor T-cells Therapy (CART)

    Will be assessed per Lugano criteria.

    Measured: 30 days after T-cell infusion, with a window of -7 to +14 days

  2. Overall Survival

    Measured: Up to 5 years post treatment

  3. Progression-free Survival

    Measured: Up to 5 years post treatment

  4. Response Rate

    Will assess response rate (complete response + partial response + stable response) following bridging prior to CART.

    Measured: Prior to (within 14 days of) lymphodepleting therapy

Timeline

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

  1. First posted6 Feb 2020
  2. Study start2 Dec 2020
  3. Primary completion7 Aug 2025
  4. Study completion1 Mar 2031 (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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04257578
Sponsor's protocol ID
RG1006269
Other IDs
NCI-2020-00238, 10418
Status last verified
May 2026
First submitted
28 Jan 2020
Last updated
25 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Acalabrutinib and Axicabtagene Ciloleucel in people with B-Cell Non-Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by University of Washington at 1 site 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 21 inclusion and 21 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: under way, not looking for participants, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 25 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (time frame: Up to 30 days post axicabtagene ciloleucel infusion). 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 NCT04257578.

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 25 Jun 2026.

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