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Mantle Cell LymphomaPhase 2NCT07910435

Polatuzumab Vedotin, Mosunetuzumab, and Acalabrutinib for the Treatment of Mantle Cell Lymphoma, PAcMan Trial

A Phase 2 study testing Polatuzumab Vedotin, Acalabrutinib and Mosunetuzumab in people with Mantle Cell Lymphoma, run by University of Washington at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial tests how well polatuzumab vedotin, mosunetuzumab, and acalabrutinib work in treating patients with mantle cell lymphoma. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a drug called monomethyl auristatin E. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Polatuzumab Vedotin, Acalabrutinib and Mosunetuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
1 Mar 2027to 1 Jan 2038
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

  • Patients ≥ 18 years of age
  • Ability to understand and willingness to sign a written informed consent document
  • Patients must have histologic confirmation of mantle cell lymphoma defined by the World Health Organization (WHO) classification and local institutional review
  • Participants must have measurable disease, defined as FDG-avid sites on baseline PET/CT measuring 1.5 cm for nodal lesions or 1 cm for extranodal lesions; and/or splenomegaly over 13 cm in largest dimension. Patients with marrow-only mantle cell lymphoma (MCL) are permitted but response assessment requires repeat bone marrow aspirate/biopsy for evaluation
  • Participants should have symptomatic disease or indication for treatment according to the treating investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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  • Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception at least 30 days prior to, during, and for at least 90 days after receiving the investigational agents
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and must agree to remain abstinent or employ contraceptive methods. Men with female partners who are WOCBP or pregnant must also agree to requirements
  • Absolute neutrophil count ≥ 1,000/mm^3 (independent of growth factor support within 7 days of testing) study entry except in cases of lymphoma involvement of the bone marrow or spleen (in which case absolute neutrophil count [ANC] of at least 500/mm^3 is required)
  • Platelets ≥ 75,000/mm^3 (independent of transfusion support within 7 days of testing) entry except in cases of lymphoma involvement of the bone marrow or spleen (in which case platelet count of at least 50,000/mm^3 is required)
  • Hemoglobin ≥ 8 g/dL (independent of transfusion support within 7 days of testing) except in cases of lymphoma involvement of the bone marrow or spleen
  • Total bilirubin < 1.5 x within normal institutional limits (unless due to Gilbert's disease, or up to 3 x upper limit of normal [ULN] if due to lymphoma involvement of liver)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal
  • Creatinine clearance ≥ 40 mL/min (as estimated by the Cockcroft-Gault equation, other method including 24-hour urine collection or nuclear medicine renal scan)

Who cannot join

  • Prior systemic therapy for MCL
  • Prior radiotherapy is permitted if measurable disease is present outside of radiation field at time of enrollment
  • Prephase therapy is permitted and may include steroids (maximum dose 1 mg/kg prednisone equivalent, for up to two weeks) prephase therapy may also be given after consent/during screening
  • Participants who are receiving other investigational agents
  • Prior solid organ transplantation or prior allogeneic hematopoietic stem cell transplantation
  • Prior treatment with a CD20/3 bispecific antibody or polatuzumab
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  • Positive coronavirus disease of 2019 (COVID-19) test within 7 days of enrollment
  • Current grade > 1 peripheral neuropathy (motor or sensory) by clinical examination or known demyelinating Charcot-Marie-Tooth disease
  • Patients with known central nervous system involvement of lymphoma
  • History of progressive multifocal leukoencephalopathy (PML)
  • Uncontrolled intercurrent illness such as: clinically significant active cardiovascular disease such as uncontrolled or symptomatic arrhythmia, uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) class III-IV, history of myocardial infarction within 6 months of screening, stroke in last 6 months, liver cirrhosis, or any other serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
  • Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast; or definitely treated, localized prostate cancer
  • Early stage prostate cancer with Gleason score 6 or below with no requirement for therapy 4
  • Patients in remission with hormone receptor-positive breast cancer on adjuvant endocrine therapy for at least 2 years prior to enrollment
  • Other cancers not specified above, that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for > 2 years without further treatment
  • Known seropositive and requiring anti-viral therapy for human immunodeficiency virus unless controlled on therapy and CD4 count is > 200/uL during screening
  • Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HbsAg] reactive or hepatitis B virus [HBV] deoxyribonucleic acid [DNA] detectable by polymerase chain reaction [PCR]) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected), or known chronic active Epstein-Barr virus (EBV)
  • History of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
  • Breastfeeding or pregnant women
  • Requires chronic treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study therapy is prohibited
  • Known active bacterial, viral, fungal, or other infection that is progressive or uncontrolled at time of screening, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of day 1 of cycle 1. Grade 1-2 infections treated with oral antibiotic therapy are not necessarily exclusionary, if they are adequately controlled per the treating investigator, and any prescribed antimicrobial therapy is complete before cycle 1 day 1 of treatment
  • Administration of a live vaccine within 4 weeks prior to start of study treatment
  • Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety or put the study at risk
  • Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication
  • History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
  • History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
  • Major surgery within 4 weeks of the first dose of study drug
  • Current therapy with warfarin or other vitamin K antagonists
  • History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Patients with a remote history of, or well-controlled autoimmune disease, may be eligible to enroll after discussion with and confirmation by the principal investigator. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study
  • Patients with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible for this study
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: Rash must cover < 10% of body surface area. Disease is well controlled at baseline and requires only low-potency topical corticosteroids. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high dose steroids within the previous 12 months

Trial locations and contacts

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

Stephen D. Smith, MD contact

206-606-6546

ssmith50@fredhutch.org

United States1 site
  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Stephen D. Smith, MD, 206-606-6546, ssmith50@fredhutch.org

    Stephen D. Smith, MD

Other trials in United States

About this study

Official title: PAcMan: Polatuzumab Vedotin, Acalabrutinib and Mosunetuzumab Response-Adapted Therapy for Previously Untreated Mantle Cell Lymphoma

This phase II trial tests how well polatuzumab vedotin, mosunetuzumab, and acalabrutinib work in treating patients with mantle cell lymphoma. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a drug called monomethyl auristatin E. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD79B receptors, and delivers monomethyl auristatin E to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. 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). 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. Giving polatuzumab vedotin, mosunetuzumab, and acalabrutinib together may be an effective treatment option for patients with mantle cell lymphoma.

Read the detailed description

OUTLINE:

INDUCTION: Patients receive polatuzumab vedotin intravenously (IV) over 30-90 minutes on day 1 of cycles 1-6, mosunetuzumab subcutaneously (SC) on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2-17, and acalabrutinib orally (PO) twice daily (BID) on days 1-21 of cycles 1-17. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve less than partial response (PR) discontinue study. Standard risk patients who achieve CR proceed to surveillance. Responding high-risk patients and responding standard risk patients who fail to achieve CR proceed to maintenance.

MAINTENANCE: Patients receive mosunetuzumab SC on day 1 of each cycle and acalabrutinib PO BID on days 1-56 of each cycle. Cycles repeat every 56 days for up to 12 cycles (cycles 18-29) in the absence of disease progression or unacceptable toxicity.

Patients undergo collection of blood samples, fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT), and core biopsy (optional) throughout the trial and undergo bone marrow aspiration (BMA) and bone marrow biopsy (BMB) at screening (optional) and on study.

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

Being tested
Polatuzumab Vedotin, Acalabrutinib, Mosunetuzumab, Bone Marrow Biopsy, Core Biopsy
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

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

  • Polatuzumab VedotinDrug

    Also called ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711

    Given IV

  • AcalabrutinibDrug

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

    Given PO

  • MosunetuzumabBiological

    Also called Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A, BTCT 4465A, BTCT-4465A, BTCT4465A

    Given SC

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Core BiopsyProcedure or surgery

    Also called BIOPSY, CORE, CNB, Core Needle, Core Needle Biopsy

    Undergo core biopsy

  • FDG-Positron Emission Tomography and Computed Tomography ScanProcedure or surgery

    Also called FDG PET/CT

    Undergo FDG PET/CT

  • Neurologic ExaminationProcedure or surgery

    Also called Nervous System Examination, Neurological Assessment, neurological exam, Neurological Examination

    Ancillary studies

  • Patient ObservationOther

    Also called Active Surveillance, deferred therapy, expectant management, Observation

    Undergo surveillance

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

Study groups in NCT07910435
Study groupRoleWhat they receive
Treatment (polatuzumab vedotin, mosunetuzumab, acalabrutinib)ExperimentalINDUCTION: Patients receive polatuzumab vedotin IV over 30-90 minutes on day 1 of cycles 1-6, mosunetuzumab SC on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2-17, and acalabrutinib PO BID on days 1-21 of cycles 1-17. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve less than PR discontinue study. Standard risk patients who achieve CR proceed to surveillance. Responding high-risk patients and responding standard risk patients who fail to achieve CR proceed to maintenance. MAINTENANCE: Patients receive mosunetuzumab SC on day 1 of each cycle and acalabrutinib PO BID on days 1-56 of each cycle. Cycles repeat every 56 days for up to 12 cycles (cycles 18-29) in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples, FDG PET/CT, and core biopsy (optional) throughout the trial and undergo BMA and BMB at screening (optional) and on study.
Receives: Drug: Polatuzumab Vedotin; Drug: Acalabrutinib; Biological: Mosunetuzumab; Procedure: Bone Marrow Biopsy; Procedure: Core Biopsy; Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan; Procedure: Neurologic Examination; Other: Patient Observation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration

What is being measured

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

  1. Positron emission tomography complete response (CR) rate

    Will consider this regimen successful and merit further investigation if the observed CR rate after 17 cycles of therapy is ≥ 85%.

    Measured: After 17 cycles of induction therapy (cycle length = 21 days)

Secondary outcomes (6)
  1. Progression-free survival

    Time to event endpoints will be estimated using the Kaplan-Meier method, and the median time to event and its corresponding 95% confidence interval will be calculated.

    Measured: From start of therapy to disease progression, or death, assessed up to 5 years

  2. Event-free survival

    Time to event endpoints will be estimated using the Kaplan-Meier method, and the median time to event and its corresponding 95% confidence interval will be calculated.

    Measured: From start of therapy to failure to achieve at least partial response, receipt of non-protocol therapy (not including maintenance or consolidation), disease progression, or death, assessed up to 5 years

  3. Overall survival

    Time to event endpoints will be estimated using the Kaplan-Meier method, and the median time to event and its corresponding 95% confidence interval will be calculated.

    Measured: From start of therapy to death from any cause, assessed up to 5 years

  4. Duration of response among patients who achieve CR or partial response (PR)

    Time to event endpoints will be estimated using the Kaplan-Meier method, and the median time to event and its corresponding 95% confidence interval will be calculated.

    Measured: From the date of first response (CR or PR) to disease progression or death, assessed up to 5 years

  5. Duration of complete response among patients who achieve CR

    Time to event endpoints will be estimated using the Kaplan-Meier method, and the median time to event and its corresponding 95% confidence interval will be calculated.

    Measured: From the date of first complete response to disease progression or death, assessed up to 5 years

  6. Incidence of adverse events

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be reported.

    Measured: Up to 90 days after last dose

Timeline

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

  1. First posted2 Nov 2026
  2. Study start1 Mar 2027 (estimated)
  3. Primary completion1 Jan 2033 (estimated)
  4. Study completion1 Jan 2038 (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
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07910435
Sponsor's protocol ID
RG1126677
Other IDs
NCI-2026-06742
Status last verified
Oct 2026
First submitted
26 Oct 2026
Last updated
2 Nov 2026
Results posted
No
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 2 study testing Polatuzumab Vedotin, Acalabrutinib and Mosunetuzumab in people with Mantle Cell Lymphoma, 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 14 inclusion and 34 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: opening soon, as of the sponsor's last update on 2 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 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 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?

Contact Stephen D. Smith, MD (206-606-6546, ssmith50@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positron emission tomography complete response (CR) rate (time frame: After 17 cycles of induction therapy (cycle length = 21 days)). 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 2 Nov 2026.

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