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Waldenström Macroglobulinemia (WM)Phase 2NCT02180724

An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia

A Phase 2 study testing Acalabrutinib (ACP-196) in people with Waldenström Macroglobulinemia (WM), run by Acerta Pharma BV at 38 sites in 7 countries.

Active, not recruiting

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and activity of acalabrutinib in treating subjects with WM. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenström Macroglobulinemia (WM)
What is being tested?
Acalabrutinib (ACP-196)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
38 sitesin 7 countries
Study dates
11 Sep 2014to 31 Dec 2026
Phase
Phase 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

  • Men and women ≥18 years of age.
  • Previously treated cohort only: A confirmed diagnosis of WM, which has relapsed after, or been refractory to ≥1prior therapy for WM and which requires treatment.
  • Previously untreated cohort only: A confirmed diagnosis of previously untreated WM in subjects who require treatment and do not want to receive chemoimmunotherapy or have comorbidities that would preclude chemoimmunotherapy such as:
  • Symptomatic hyperviscosity with an IgM ≥5,000mg/dL
  • Disease-related neuropathy
  • Serum concentration of IgM, as measured by SPEP and IFE, that exceeds the upper limits of normal or measurable nodal WM (defined as the presence of ≥1lymph node that measures ≥2.0 cm in the longest diameter and ≥1.0cm in the longest perpendicular diameter).
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  • ECOG performance status of ≤2.
  • Women who are sexually active and can bear children must agree to use highly effective forms of contraception during 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 without difficulty.
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

Who cannot join

  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥2 years or which will not limit survival to <2 years. Note: These cases must be discussed with the medical monitor.
  • A life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
  • 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, or QTc >480 msec.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Any immunotherapy within 4 weeks of first dose of study drug.
  • For subjects with recent chemotherapy or experimental therapy, the first dose of study drug must occur after 5 times the half-life of the agent(s).
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  • Prior exposure to a BCR inhibitor (e.g., BTK,PI3K, or SYK inhibitors) or BCL-2 inhibitors (e.g., ABT-199).
  • Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment of WM or other conditions. Note: Subjects may use topical or inhaled corticosteroids or low-dose steroids (≤10 mg of prednisone or equivalent per day) as therapy for comorbid conditions. During study participation, subjects may also receive systemic or enteric corticosteroids as needed for treatment-emergent comorbid conditions.
  • Grade ≥2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.
  • Known history of HIV or active infection with HCV or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
  • Major surgery within 4 weeks before first dose of study drug.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • History of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).
  • History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 28 days of first dose of study drug.
  • Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
  • ANC <0.75 x 109/L or platelet count <50 x 109/L. For subjects with disease involvement in the bone marrow, ANC <0.50 x 109/L or platelet count <30x109/L.
  • Creatinine >2.5 x institutional ULN; total bilirubin >2.5 x ULN; or AST or ALT >3.0 x ULN.
  • Lactating or pregnant.
  • Concurrent participation in another therapeutic clinical trial.

Trial locations and contacts

38 sites in 7 countries.

38 sites in 7 countries

France13 sites

  • Research Site

    Aurillac, 15002

  • Research Site

    Clermond Ferrand, 63003

  • Research Site

    Marseille, 13273

  • Research Site

    Montpellier, 34295

  • Research Site

    Nantes, 44093

  • Research Site

    Paris, 75015

  • Research Site

    Paris, 75651

  • Research Site

    Pierre-Bénite, 69495

  • Research Site

    Poitiers, 86021

  • Research Site

    Reims, 51092

  • Research Site

    Rennes, 35000

  • Research Site

    Toulouse, 31059

  • Research Site

    Vandœuvre-lès-Nancy, 54500

Other trials in France

United States10 sites

  • Research Site

    Aurora, Colorado, 80012

  • Research Site

    Austin, Texas, 78705

  • Research Site

    Bedford, Texas, 76022

  • Research Site

    Houston, Texas, 77030

  • Research Site

    Minneapolis, Minnesota, 55404

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    New York, New York, 10021

  • Research Site

    Santa Barbara, California, 93105

  • Research Site

    Vancouver, Washington, 98684

  • Research Site

    Washington D.C., District of Columbia, 20007

Other trials in United States

United Kingdom8 sites

  • Research Site

    Bournemouth, BH7 7DW

  • Research Site

    Leeds, LS9 7TF

  • Research Site

    Leicester, LE1 7RH

  • Research Site

    London, NW1 2BU

  • Research Site

    London, SW3 6JJ

  • Research Site

    Oxford, OX3 7LE

  • Research Site

    Plymouth, PL6 8DH

  • Research Site

    Southampton, SO16 6YD

Other trials in United Kingdom

Italy3 sites

  • Research Site

    Bologna, 40138

  • Research Site

    Milan, 20162

  • Research Site

    Novara, 28100

Other trials in Italy

Netherlands2 sites

  • Research Site

    Amsterdam, 1105AZ

  • Research Site

    Utrecht, 2508GA

Other trials in Netherlands

Greece1 site

  • Research Site

    Athens, 11528

Other trials in Greece

Spain1 site

  • Research Site

    Salamanca, 37007

Other trials in Spain

About this study

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and activity of acalabrutinib in treating subjects with WM.

Read the detailed description

Clinical studies have shown that targeting the B-cell receptor (BCR) signaling pathway by inhibiting Bruton tyrosine kinase (BTK) produces significant clinical benefit in patients with non-Hodgkin lymphoma, including Waldenström macroglobulinemia (WM). Ibrutinib (IMBRUVICA®), an oral, small-molecule BTK inhibitor has been approved for the treatment for chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and WM.

Acerta Pharma BV (AcertaPharma) has developed a novel BTK inhibitor, acalabrutinib, that achieves significant oral bioavailability and potency in preclinical models.

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and activity of acalabrutinib in treating subjects with WM.

Being tested
Acalabrutinib (ACP-196)
Keywords
Bruton tyrosine kinase inhibitor, Btk, Waldenström Macroglobulinemia, WM, Waldenström, Macroglobulinemia
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • Acalabrutinib (ACP-196)Drug

    Also called Acalabrutinib

  • Acalabrutinib (ACP-196)Drug

    Also called Acalabrutinib

Study groups in NCT02180724
Study groupRoleWhat they receive
Previously TreatedExperimentalSubjects previously treated with Waldenström Macroglobulinemia N=92
Receives: Drug: Acalabrutinib (ACP-196)
Treatment NaïveExperimentalSubjects with treatment-naïve Waldenström Macroglobulinemia. N=14
Receives: Drug: Acalabrutinib (ACP-196)

What is being measured

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

  1. Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria

    ORR defined as the rate of subjects achieving a Miner Response (MR) or better including complete response (CR), very good partial response (VGPR), partial response (PR) and MR; The definition of responses are evaluated by investigators using both Modified 6th criteria (refer to protocol table 4-2 , 4-3) and Modified 3rd International Workshop of Waldenström Macroglobulinemia (IWWM) criteria (refer to protocol table 4-4 and table 4-5 for definition). For Modified 6th criteria, MR is defined as (1) monoclonal IgM protein is detectable, (2) no new signs or symptoms of active disease, (3) and patient has >=25% but < 50% reduction in serum monoclonal IgM level from baseline. PR and VGPR both require (1) and (2) as MR, but PR also requires the >=50% and <90% reduction in serum monoclonal IgM level as well as reduction in extramedullary disease. VGPR requires >= 90% reduction in serum IgM and complete resolution of extramedullary disease.

    Measured: Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

  2. Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria

    ORR defined as the rate of subjects achieving a Miner Response (MR) or better including complete response (CR), very good partial response (VGPR), partial response (PR) and MR; The definition of responses are evaluated by investigators using both Modified 6th criteria (refer to protocol table 4-2 , 4-3) and Modified 3rd International Workshop of Waldenström Macroglobulinemia (IWWM) criteria (refer to protocol table 4-4 and table 4-5 for definition). For Modified 6th criteria, MR is defined as (1) monoclonal IgM protein is detectable, (2) no new signs or symptoms of active disease, (3) and patient has >=25% but < 50% reduction in serum monoclonal IgM level from baseline. PR and VGPR both require (1) and (2) as MR, but PR also requires the >=50% and <90% reduction in serum monoclonal IgM level as well as reduction in extramedullary disease. VGPR requires >= 90% reduction in serum IgM and complete resolution of extramedullary disease.

    Measured: Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

Secondary outcomes (3)

  1. Progression-free Survival (PFS) of Acalabrutinib by Investigator

    Kaplan-Meier (K-M) estimates of the PFS assessments and its 95% confidence interval are provided using both modified 3rd and 6th IWWM criteria by investigator. K-M estimates at a certain time (ex. all subjects complete Cycle 27) provides the estimated percentage of the subjects who are still alive or have not progressed by the given time over all patients at risk. Per 6th IWWM criteria, the progressive disease is defined as >= 25% increase in serum IgM level with an absolute increase of at least 500 mg/dL from lowest nadir (requires confirmation on at least 2 consecutive measurements at least 4 weeks apart) and/or progression of clinical features attributable to the disease. Per modified 3rd IWWM criteria, besides IgM requirement as 6th criteria, it could also includes progression of clinically significant disease related symptoms and/or death from any cause or initiation of a new anti-neoplastic therapy.

    Measured: Up to approximately 3.8 years. Data cut at last subject have completed Cycle 27 (28 days per Cycle).

  2. Overall Survival (OS) of Acalabrutinib by Investigator

    Outcome Measure was pre-specified to summarize data per investigator assessment with respect to subject's vital/survival status is presented in the RRF and irrespective of iWWM 3rd or 6th criteria. Kaplan-Meier (K-M) estimates at a certain time (ex. all subjects complete Cycle 27) provides the estimated percentage of the subjects who are still alive by the given time over all patients at risk.

    Measured: Primary analysis occur when all subjects have completed Cycle 27 or have discontinued before Cycle 27.

  3. Summary of Duration of Response (DOR)

    DOR is defined as the interval from the first documentation of Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR) or Minor Response (MR) to the earlier of the first documentation of definitive PD or death from any cause. The summary statistics are provided for DOR.

    Measured: Primary analysis occur when all subjects have completed Cycle 27 or have exit the study

Timeline

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

  1. First posted3 Jul 2014 (estimated)
  2. Study start11 Sep 2014
  3. Primary completion1 Oct 2019
  4. Study completion31 Dec 2026 (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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02180724
Sponsor's protocol ID
ACE-WM-001
Other IDs
2023-509356-34-00, 2014-003212-36, 2014, 2023
Status last verified
Sep 2026
First submitted
30 Jun 2014
Last updated
14 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

  • Owen RG, McCarthy H, D'Sa S, Thomas SK, Tournilhac O, Forconi F, Kersten MJ, Zinzani PL, Iyengar S, Kothari J, Minnema MC, Kastritis E, Cheson BD, Walter HS, Greenwald D, Calvo R, Li Y, Rule S, Furman RR. Acalabrutinib in Waldenstrom macroglobulinemia yields durable responses with 5 years of follow-up. Blood Adv. 2026 Jul 28;10(14):5058-5069. doi: 10.1182/bloodadvances.2025017713.

    PubMed 41985004

  • Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.

    PubMed 39563886

  • Owen RG, McCarthy H, Rule S, D'Sa S, Thomas SK, Tournilhac O, Forconi F, Kersten MJ, Zinzani PL, Iyengar S, Kothari J, Minnema MC, Kastritis E, Aurran-Schleinitz T, Cheson BD, Walter H, Greenwald D, Chen DY, Frigault MM, Hamdy A, Izumi R, Patel P, Wei H, Lee SK, Mittag D, Furman RR. Acalabrutinib monotherapy in patients with Waldenstrom macroglobulinemia: a single-arm, multicentre, phase 2 study. Lancet Haematol. 2020 Feb;7(2):e112-e121. doi: 10.1016/S2352-3026(19)30210-8. Epub 2019 Dec 19.

    PubMed 31866281

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib (ACP-196) in people with Waldenström Macroglobulinemia (WM), run by Acerta Pharma BV at 38 sites in 7 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 10 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 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in France, United States, United Kingdom, Italy, Netherlands and 2 more countries. 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?

Yes. Results are posted in the registry (first posted 24 Apr 2020). 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?

Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 6th Criteria (time frame: Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).). 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 NCT02180724, which also lists 3 linked publications.

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 14 Sep 2026.

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