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Diffuse Large B-Cell LymphomaPhase 1/2NCT05256641

Acalabrutinib Maintenance for the Treatment of Patients With Large B-cell Lymphoma

A Phase 1/2 study testing Acalabrutinib in people with Diffuse Large B-Cell Lymphoma and High-grade B-cell Lymphoma, run by Jonsson Comprehensive Cancer Center at 3 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
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Trial summary

This phase Ib/II trial studies the side effects and efficacy of maintenance acalabrutinib following cellular therapy in treating patients with large B-cell lymphoma at very high risk of the cancer coming back. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
3 sitesUnited States
Study dates
23 Jan 2023to 31 Jan 2028
Phase
Phase 1/2
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ages 18-70 years
  • One of the following:
  • Patients undergoing autologous stem cell transplantation (ASCT) or any Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T-cell therapy product for:
  • High grade B-cell lymphoma (double or triple hit) with rearrangements in bcl-2 and/or bcl-6, and rearrangement in myc
  • Large B-cell lymphoma with a history of secondary CNS involvement
  • Histologic transformation of indolent lymphoma to large B-cell lymphoma, including marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic leukemia, or Waldenstrom macroglobulinemia
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  • High risk international prognostic index (IPI) score 4 or 5, at diagnosis or prior to CAR T-cell leukapheresis
  • Patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for large B-cell lymphoma
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Requirements for post-ASCT and post-alloHCT participants:
  • Disease status of partial response (PR) or complete response (CR) prior to transplantation
  • Receive reduced-intensity conditioning regimen
  • Enrollment no later than day +90
  • Requirements for post-CAR T-cell therapy participants:
  • Disease status of PR or CR after post-CAR T-cell therapy positron emission tomography (PET)-computed tomography (CT) at 1-3 months
  • Enrollment no later than day +104
  • Ability to give full informed consent
  • Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib
  • Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty
  • Absolute neutrophil count (ANC) > 500/uL (microliters)
  • Platelets > 50,000/uL independent of transfusions
  • Hemoglobin > 8 g/dL independent of transfusions
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN, unless directly attributable to Gilbert's syndrome
  • Creatinine clearance >= 60 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) and serum creatinine (Cr) =< 1.8 mg/dL

Who cannot join

  • Cord blood as donor source in alloHCT
  • New York Heart Association Class III or IV
  • Left ventricular ejection fraction < 50%
  • Estimated glomerular filtration rate < 30 mL/min
  • Concurrent long-term use of posaconazole or other strong CYP3A4 inhibitors and unable to replace with equivalent medication
  • Acute or chronic graft-versus-host disease (GvHD) >= stage 3 at time of enrollment
Show all 21Show fewer
  • Received packed red blood cells (pRBC) transfusion within the past 2 weeks
  • Received platelet transfusion within the past 1 week
  • Active invasive fungal infection
  • Active bacterial or viral infection until resolution of the infection
  • History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
  • Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
  • Major surgical procedure within 30 days before the 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
  • Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment
  • Received a live virus vaccination within 28 days of first dose of study drug
  • Known history of infection with human immunodeficiency virus (HIV)
  • History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
  • Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
  • Breastfeeding or pregnant
  • Concurrent participation in another therapeutic clinical trial

Trial locations and contacts

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

United States3 sites, 3 recruiting
  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

    Vlad Kustanovich, 310-206-5756, VKustanovich@mednet.ucla.edu

    Caspian Oliai, MD

    Recruiting
  • University of Oklahoma

    Oklahoma City, Oklahoma, 73190

    Matthew J. Wieduwilt, 405-217-8001, Matthew-Wieduwilt@ouhsc.edu

    Matthew J. Wieduwilt

    Not yet recruiting
  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Joseph M. Tuscano, 916-734-3772, jtuscano@ucdavis.edu

    Joseph M. Tuscano

    Recruiting

Other trials in United States

About this study

Official title: Acalabrutinib Maintenance Following Cellular Therapy for Large B-Cell Lymphoma Patients at Very High Risk for Relapse

This phase Ib/II trial studies the side effects and efficacy of maintenance acalabrutinib following cellular therapy in treating patients with large B-cell lymphoma at very high risk of the cancer coming back. Acalabrutinib is a small molecular inhibitor that may interfere with the ability of cancer cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety and tolerability of maintenance acalabrutinib following cellular therapy in participants with large B-cell lymphoma at very high risk for relapse.

SECONDARY OBJECTIVES:

  1. To estimate the effectiveness of maintenance acalabrutinib following cellular therapy in participants with large B-cell lymphoma at high risk for relapse.

II. To estimate the durability of remission after completion of acalabrutinib maintenance.

III. To estimate survival following completion of acalabrutinib maintenance. IV. To estimate the rate of conversion from partial response (PR) following chimeric antigen receptor (CAR) T-cell therapy to complete response (CR) after the addition of acalabrutinib maintenance.

  1. To estimate rates of dose reductions, dose pauses, and permanent discontinuations of acalabrutinib that occur post-cellular therapy.

VI. To estimate the rate of stage >= 2 graft-versus-host disease in participants receiving acalabrutinib post-allogeneic hematopoietic cell transplantation (alloHCT).

VII. To estimate the rates of grade 2, 3, and 4 hematologic toxicity in participants receiving acalabrutinib post-cellular therapy.

VIII. To estimate the rates of grade 2, 3, and 4 non-hematologic toxicity in participants receiving acalabrutinib post-cellular therapy.

EXPLORATORY OBJECTIVES:

  1. To evaluate CAR T-cell persistence in the setting of acalabrutinib. II. To evaluate changes in immunophenotype of peripheral blood mononuclear cells before and after initiation of acalabrutinib, and changes at time of relapse.

III. To evaluate changes in circulating tumor deoxyribonucleic acid (ctDNA), intracellular cytokine and phospho-protein profiling of peripheral blood mononuclear cells before and after initiation of acalabrutinib, and changes at time of relapse.

IV. To determine if there are signs of central nervous system (CNS) penetration of acalabrutinib.

OUTLINE: Patients are assigned to 1 of 3 groups.

GROUP I (ALLOHCT GROUP): Beginning day 90, patients receive acalabrutinib orally (PO) once daily (QD) and then( orally, twice daily (PO BID) once no longer on prophylactic antifungal (CYP34A inhibitors) until day 365 in the absence of disease progression or unacceptable toxicity.

GROUP II (AUTOLOGOUS STEM CELL TRANSPLANTATION [ASCT] GROUP): Beginning day 60, patients receive acalabrutinib PO QD and then PO BID from day 74 if there are no dose reductions until day 365 in the absence of disease progression or unacceptable toxicity.

GROUP III (CAR-T CELL THERAPY GROUP): Beginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Acalabrutinib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • AcalabrutinibDrug

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

    Given PO

Study groups in NCT05256641
Study groupRoleWhat they receive
Group I (acalabrutinib)ExperimentalBeginning day 90, patients receive acalabrutinib PO QD and then PO BID once no longer on prophylactic antifungal (CYP34A inhibitors) until day 365 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acalabrutinib
Group II (acalabrutinib)ExperimentalBeginning day 60, patients receive acalabrutinib PO QD and then PO BID from day 74 if there are no dose reductions until day 365 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acalabrutinib
Group III (acalabrutinib)ExperimentalBeginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acalabrutinib

What is being measured

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

  1. Permanent discontinuation of acalabrutinib

    Tolerability will be determined by the number of patients who permanently discontinue acalabrutinib within 12 months from cellular therapy due to intolerance. The proportion of patients with acalabrutinib discontinuation will be reported along with 95% and 90% confidence intervals.

    Measured: Up to 12 months from cellular therapy

Secondary outcomes (8)
  1. Progression-free survival (PFS)

    The 1-year PFS will be evaluated based on progression of disease per Lugano criteria or death, and will be reported based on Kaplan-Meier estimates along with 95% confidence interval.

    Measured: At 12 months from cellular therapy

  2. PFS

    Will be reported based on 95% confidence intervals at annual time points.

    Measured: Up to 5 years

  3. Overall survival

    Time from cellular therapy to death due to any cause, assessed at 1 and 5 years based on Kaplan-Meier estimates along with 95% confidence interval

    Measured: Up to 5 years

  4. Rate of conversion from partial response following chimeric antigen receptor (CAR) T-cell therapy to complete response after the addition of acalabrutinib maintenance

    Will be reported based on 95% confidence intervals.

    Measured: Up to day 365

  5. Incidence of dose reductions, interruptions, or discontinuations of acalabrutinib based on the protocol criteria

    Will be reported based on 95% confidence intervals.

    Measured: Up to day 365

  6. Incidence of graft versus host disease (GvHD) >= stage 2

    Based on the Mount Sinai Acute GVHD International Consortium criteria for acute GvHD and the National Institutes of Health consensus criteria for chronic GvHD. Will be reported based on 95% confidence intervals.

    Measured: Up to day 365

  7. Incidence of hematologic adverse events

    Based on Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Will be reported based on 95% confidence intervals.

    Measured: Up to day 365

  8. Incidence of non-hematologic adverse events

    Based on CTCAE v5.0. Will be reported based on 95% confidence intervals.

    Measured: Up to day 365

Timeline

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

  1. First posted25 Feb 2022
  2. Study start23 Jan 2023
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion31 Jan 2028 (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
Parallel groups
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05256641
Sponsor's protocol ID
21-000979
Other IDs
NCI-2021-12421
Status last verified
Mar 2026
First submitted
4 Jan 2022
Last updated
10 Mar 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 1/2 study testing Acalabrutinib in people with Diffuse Large B-Cell Lymphoma and High-grade B-cell Lymphoma, run by Jonsson Comprehensive Cancer Center at 3 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 25 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: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 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?

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?

Contact Vlad Kustanovitch (310-206-5756, VKustanovich@mednet.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Permanent discontinuation of acalabrutinib (time frame: Up to 12 months from cellular therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 10 Mar 2026.

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