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Diffuse Large B-cell LymphomaPhase 2NCT04604067

Assessing a ctDNA and PET-oriented Therapy in Patients With DLBCL A Multicenter, Open-label, Phase II Trial.

A Phase 2 study testing Acalabrutinib in people with Diffuse Large B-cell Lymphoma, run by Swiss Cancer Institute at 19 sites in 2 countries.

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

Within this exploratory multicohort phase II trial, SAKK aims to evaluate a PET/CT and ctDNA oriented therapy in DLBCL in order to test the following working hypothesis. acalabrutinib-R-CHOP may improve the progression free survival in genetically defined DLBCL harboring the MYD88 L265P and/or CD79A/B mutations… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Acalabrutinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
260 participants
Where
19 sitesin 2 countries
Study dates
25 Jun 2021to Dec 2030
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

  • Written informed consent according to ICH GCP E6(R2) regulations before registration and prior to any trial specific procedures.
  • Histologically confirmed, treatment-naïve DLBCL, NOS that fulfill all the following:
  • Patient eligible for 6 cycles of R-CHOP
  • Ann Arbor stage I-IV
  • Metabolically active measurable disease by 18FDG PET-CT
  • No previous treatment with systemic chemotherapy or radiotherapy (a pre-phase treatment with steroids for up to a total of 10 days is allowed; baseline PET/CT, liquid biopsy and bone marrow biopsy and aspirate must be collected either before or within a maximum of 5 days after steroid pre-phase treatment starts. If a patient receives steroids, glucose levels must be checked and be normal on the day of PET/CT before the exam.
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  • At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions.
  • Quantifiable and qualifiable circulating tumor DNA
  • Patients with a prior malignancy and treated with curative intention are eligible if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease at registration. Less than 2 years is acceptable for malignancies with low risk of recurrence and/or no late recurrence.
  • Age ≥ 18 years
  • EGOG performance status 0-2 (or 3 if due to disease)
  • Adequate bone marrow function: neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L (unless due to bone marrow involvement: in this case the permitted limit is ≥ 50 x 109/L) with allowed premedication or supportive medication.
  • Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST, ALT ≤ 2.5 x ULN, or ≤ 5 x ULN under the assumption that abnormal values are a result of liver involvement by lymphoma
  • Adequate renal function: estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 (according to CKD-EPI formula)
  • Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 50% as determined by echocardiography (ECHO)
  • Adequate coagulation function: INR ≤ 1.5 x ULN (the ULN for INR is defined with the value 1.2 for all sites, in case no ULN is documented in the lab certificates/sheets), aPTT ≤ 1.5 x ULN.
  • Women of childbearing potential must use highly effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and until 12 months after the last dose of investigational drug. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential. (www.swissmedicinfo.ch).
  • Men agree not to donate sperm or to father a child during trial treatment and until 12 months after the last dose of investigational drug
  • Patient is able and willing to swallow trial drug as whole capsule or tablet.
  • Patient is willing to participate in translational research projects

Who cannot join

  • CNS lymphoma involvement
  • Stage I disease that has been completely surgically excised (not measurable)
  • Specific diagnostic categories of large B-cell lymphoma such as high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, primary central nervous system lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, intravascular large B-cell lymphoma, plasmablastic lymphoma, lymphomatoid granulomatosis, primary effusion lymphoma or transformed lymphoma etc.
  • Concomitant treatment with any other experimental drug
  • Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV; unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of asymptomatic or rate controlled atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension.
  • Uncontrolled systemic infection.
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  • History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
  • History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration
  • History of bleeding diathesis (eg, haemophilia, von Willebrand disease).
  • Major surgery in the preceding 4 weeks of first dose of study drug. 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.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass.
  • History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis.
  • Known history of human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations. All patients must be screened for hepatitis up to 28 days prior to study drug start using the routine hepatitis virus laboratory panel. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy and have HBV-DNA testing every 4 months. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
  • Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent.
  • Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon), 'dual' antiplatelet therapy (DAPT), such as aspirin and clopidogrel. However, use of therapeutic low molecule weight heparin, direct oral anticoagulants, or low dose anti-platelet agents is allowed.
  • Concomitant treatment to acalabrutinib capsules or tablets with strong CYP3A inducers or strong CYP3A inhibitors. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of acalabrutinib is prohibited.
  • Co-administration of acalabrutinib capsules with proton pump inhibitors (PPIs).
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
  • Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
  • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Trial locations and contacts

19 sites in 2 countries.

19 sites in 2 countries

Switzerland16 sites

  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden (Baden/Brugg)

    Baden, 5404

  • St. Claraspital

    Basel, 4058

  • Istituto Oncologico della Svizzera Italiana

    Bellinzona, 6500

  • Inselspital, Bern

    Bern, CH-3010

  • Kantonsspital Graubünden

    Chur, 7000

  • Hopital Fribourgeois

    Fribourg, 1708

  • Hopitaux Universitaire de Genève (HUG)

    Geneva, 1211

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Kantonsspital Luzern

    Luzerne, CH-6000

  • Réseau Hospitalier Neuchâtelois (RHNe)

    Neuchâtel, 2000

  • Kantonsspital Olten

    Olten, CH-4600

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Kantonsspital Winterthur

    Winterthur, 8401

  • UniversitätsSpital Zürich

    Zurich, 8091

  • City Hospital Triemli

    Zurich, CH-8063

Other trials in Switzerland

Italy3 sites

  • Ospedale Papa Giovanni XXIII

    Bergamo, 24127

  • Azienda Ospedaliera Universitaria Maggiore della Carita di Novara

    Novara, 20503

  • Policlinico Agostino Gemelli

    Roma, 00168

Other trials in Italy

About this study

Official title: Assessing a Circulating Tumor (ctDNA) and Positron Emission Tomography (PET)-Oriented Therapy in Patients With Diffuse Large B-cell Lymphoma (DLBCL). A Multicenter, Open-label, Phase II Trial.

Within this exploratory multicohort phase II trial, SAKK aims to evaluate a PET/CT and ctDNA oriented therapy in DLBCL in order to test the following working hypothesis.

  • acalabrutinib-R-CHOP may improve the progression free survival in genetically defined DLBCL harboring the MYD88 L265P and/or CD79A/B mutations;
  • treatment escalation to acalabrutinib-R-CHOP in DLBCL patients who have positive PET/CT (with residual disease scored as Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 reduction of ctDNA) after two courses of R-CHOP could improve the anti-tumour activity of R-CHOP;
  • treatment de-escalation to 4 total R-CHOP courses plus 2 rituximab single agent infusions does not compromise the outcome in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP.
Read the detailed description

Despite advances in the clinical care of patients with DLBCL and in understanding the biology of this disease, cure rates have remained the same since the introduction of rituximab to CHOP chemotherapy, and R-CHOP chemoimmunotherapy remains the standard of care. Over the last years many phase III trials investigating new agents added to R-CHOP have been performed but they have all invariably failed to improve treatment outcomes. Importantly, three of the most recently completed phase III trials that were developed based on the cell of origin distinction of DLBCL and aimed to improve treatment outcome in the ABC (or non- Germinal center B-Cell (GCB)) subtype by adding a targeted agent to R-CHOP have also failed. This provides clinical evidence that cell of origin may not be an accurate biomarker for treatment decisions. The R - CHOP + investigational drug approach has thus failed either when broadly applied to unselected DLBCL patients or when applied to DLBCL patients selected according to inaccurate biomarkers such as COO.

Within this exploratory multicohort phase II trial, SAKK aims to evaluate a PET/CT and ctDNA oriented therapy in DLBCL in order to test the following working hypothesis.

  • acalabrutinib-R-CHOP may improve the progression free survival in genetically defined DLBCL harboring the MYD88 L265P and/or CD79A/B mutations;
  • treatment escalation to acalabrutinib-R-CHOP in DLBCL patients who have positive PET/CT (with residual disease scored as Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 reduction of ctDNA) after two courses of R-CHOP could improve the anti-tumour activity of R-CHOP;
  • treatment de-escalation to 4 total R-CHOP courses plus 2 rituximab single agent infusions does not compromise the outcome in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two courses R-CHOP.

Primary objectives:

  • Assessing the efficacy of acalabrutinib-R-CHOP in DLBCL harboring MYD88 L265P and/or CD79A/B mutations (cohort A)
  • Assessing the activity of treatment escalation to acalabrutinib-R-CHOP followed by acalabrutinib monotherapy in DLBCL patients who are double positive: PET/CT positive (Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 fold reduction) after two courses of R-CHOP (cohort B)
  • Exploring the feasibility of treatment de-escalation to 4 total R-CHOP courses plus two infusions of single agent rituximab in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP (cohort C).
  • Exploring clinical implications of having a negative PET/CT (Deauville score 1-3) but no molecular response (<2log10 reduction of ctDNA) vs a positive PET/CT (Deauville score 4 or 5 with centrally defined response) but molecular response (>2log10 reduction of ctDNA) after two R-CHOP courses (cohort D)

Secondary objectives:

  • Safety and tolerability of acalabrutinib-R-CHOP
  • Assessment of prognostic value of baseline PET radiomics indexes, alone or in association with other parameters
Being tested
Acalabrutinib
Keywords
Diffuse large B-cell lymphoma, Circulating tumor DNA (ctDNA), PET-oriented therapy, acalabrutinib-R-CHOP, 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

    Cohort A: 6 cycles of acalabrutinib-R-CHOP

    Cohort B: 2 cycles of R-CHOP and 2 cycles of acalabrutinb-R-CHOP followed by 2 cycles of acalabrutinib single agent

    Cohort C: 4 cycles of R-CHOP followed by 2 cycles of rituximab single agent

    Cohort D: 6 cycles of R-CHOP

    Rituximab 375 mg/m2 IV Day 1, cyclophosphamide 750 mg/m2 IV Day 1, doxorubicin 50 mg/m2 IV Day 1, vincristine 1.4 mg/m2 (maximum 2 mg) IV Day 1; prednisone 100 mg PO d1-5; Acalabrutinib 100 mg BID Day 1-21, cycles repeated every 21 days

Study groups in NCT04604067
Study groupRoleWhat they receive
Arm with 4 cohortsExperimentalCohort A: MYD88 L265P and/or CD79A/B mutations at baseline Treatment: Acalabrutinib-R-CHOP for a total number of 6 cycles. Cohort B, C D: Without MYD88 L265P and CD79A/B mutations at baseline: Assignment of cohort B, C and D after 2 cycles of R-CHOP according to PET (Deauville score (DS)) and molecular response (MR) (>2log10 reduction of ctDNA) results: Cohort B: DS 4 and No MR Treatment: 2 cycles of acalabrutinib-R-CHOP. After PET3/ctDNA3: patients with DS 1-3 and no MR OR DS4 with MR will receive 2 additional cycles of acalabrutinb-R-CHOP and 2 cycles of acalabrutinib single agent. Cohort C: DS 1-3 and MR Treatment: 2 additional cycles of R-CHOP (4x RCHOP in total) followed by 2 cycles of rituximab single agent. Cohort D: DS 4 and no MR OR DS 1-3 and MR Treatment: 4 additional cycles of RCHOP (6 cycles in total). Follow up: Patients off treatment will be followed for 5 years.
Receives: Drug: Acalabrutinib

What is being measured

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

  1. Cohorts A, C and D: Progression free survival (PFS) according to the Lugano criteria

    PFS is defined as the time from registration until the first event of interest:

    • Progressive disease according to the Lugano Classification
    • Death from any cause

    Patients not having an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last tumor assessment showing non-progression before starting a new treatment.

    Measured: from registration until the first event as defined in PFS (estimated 2 years)

  2. Cohort B: Complete remission (CR) rate at the end of therapy according to the Lugano criteria

    Patients with CR at the end of therapy will be considered CR. Patients with no tumor assessment at the end of therapy will be considered:

    • non-CR, if they have no following tumor assessment within the trial (patient died, refused, started a new treatment or was lost to follow-up) or if they have non-CR at the following tumor assessment after the end of therapy.
    • CR, if they have CR at the following tumor assessment after end of therapy before starting a new treatment.

    Measured: estimated 9 months after registration

Secondary outcomes (6)

  1. Adverse events (AEs)

    All AEs will be assessed according to NCI CTCAE v5.0.

    Measured: record throughout treatment phase (until 28 days after last dose of trial treatment)

  2. Overall survival (OS)

    OS will be calculated from registration until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.

    Measured: from registration to date of death from any cause (estimated 5 years)

  3. Progression free survival in cohort B

    Analogous to the evaluation of the primary endpoint of cohorts A, C and D, but in cohort B.

    Measured: from registration until the first event as defined in PFS (estimated 2 years)

  4. Complete remission rate in cohorts A, C and D

    Analogous to the evaluation of the primary endpoint of cohort B, but in cohorts A, C and D.

    Measured: estimated 9 months after registration

  5. Overall response rate (ORR)

    ORR at the end of therapy is defined as either PR or CR (OR) according to the Lugano criteria. Patients with no tumor assessment at the end of therapy will be considered:

    • non-OR, if they have no following tumor assessment within the trial (patient died, refused, started a new treatment or was lost to follow-up) or if they have non-OR at the following tumor assessment after the end of therapy.
    • OR, if they have OR at the following tumor assessment after end of therapy before starting a new treatment

    Measured: estimated 9 months after registration

  6. Duration of response (DoR)

    The DoR will be calculated from when the criteria for CR or PR are met, until documentation of progressive disease thereafter. Only patients with a CR or PR will be included in this analysis. Patients without any documentation of progressive disease thereafter will be censored at the last date of tumor assessment without progression and before the start of a new anti-lymphoma treatment, if any.

    Measured: estimated 2 years

Timeline

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

  1. First posted27 Oct 2020
  2. Study start25 Jun 2021
  3. Primary completion30 Jan 2029 (estimated)
  4. Study completionDec 2030 (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
Model description
All patients will have a PET/CT (PET1) and evaluation of circulating tumor DNA (ctDNA1) at baseline. The trial consists of four treatment cohorts (cohorts A, B, C and D) and a first assignment to treatment will be done at baseline based on the presence or absence of MYD88 L265P and/or CD79A/B mutations.
Masking
None (open label)
Enrolment
260 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04604067
Sponsor's protocol ID
SAKK 38/19
Other IDs
2020-003876-42
Status last verified
Oct 2026
First submitted
22 Oct 2020
Last updated
21 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib in people with Diffuse Large B-cell Lymphoma, run by Swiss Cancer Institute at 19 sites in 2 countries.

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 20 inclusion and 20 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 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Switzerland, Italy. 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?

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?

Cohorts A, C and D: Progression free survival (PFS) according to the Lugano criteria (time frame: from registration until the first event as defined in PFS (estimated 2 years)). 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 NCT04604067.

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 21 Oct 2026.

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