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

NCT ID: NCT02180724

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-11
• Study Completion Date: 2026-12-31

Brief Summary

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

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.

Conditions

Waldenström Macroglobulinemia (WM)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Previously Treated

Subjects previously treated with Waldenström Macroglobulinemia N=92

Group Type: EXPERIMENTAL

Acalabrutinib (ACP-196)

Intervention Type: DRUG

Treatment Naïve

Subjects with treatment-naïve Waldenström Macroglobulinemia. N=14

Group Type: EXPERIMENTAL

Acalabrutinib (ACP-196)

Intervention Type: DRUG

Interventions

Acalabrutinib (ACP-196)

Intervention Type: DRUG

Acalabrutinib (ACP-196)

Intervention Type: DRUG

Other Intervention Names

Acalabrutinib; Acalabrutinib

Eligibility Criteria

Inclusion Criteria

1. Men and women ≥18 years of age.

2. 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.

3. 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

4. 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).

5. ECOG performance status of ≤2.

6. 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.

7. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.

8. 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).

Exclusion Criteria

1. 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.

2. 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.

3. 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.

4. 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.

5. Any immunotherapy within 4 weeks of first dose of study drug.

6. 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).

7. Prior exposure to a BCR inhibitor (e.g., BTK,PI3K, or SYK inhibitors) or BCL-2 inhibitors (e.g., ABT-199).

8. 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.

9. Grade ≥2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.

10. Known history of HIV or active infection with HCV or hepatitis B virus (HBV) or any uncontrolled active systemic infection.

11. Major surgery within 4 weeks before first dose of study drug.

12. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.

13. History of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).

14. History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.

15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 28 days of first dose of study drug.

16. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).

17. 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.

18. Creatinine >2.5 x institutional ULN; total bilirubin >2.5 x ULN; or AST or ALT >3.0 x ULN.

19. Lactating or pregnant.

20. Concurrent participation in another therapeutic clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acerta Pharma BV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AstraZeneca Clinical study Information Center

Role: STUDY_DIRECTOR

1-877-240-9479 information.center@astrazeneca.com

Locations

Research Site

Santa Barbara, California, United States

Research Site

Aurora, Colorado, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Minneapolis, Minnesota, United States

Research Site

New York, New York, United States

Research Site

Nashville, Tennessee, United States

Research Site

Austin, Texas, United States

Research Site

Bedford, Texas, United States

Research Site

Houston, Texas, United States

Research Site

Vancouver, Washington, United States

Research Site

Aurillac, , France

Research Site

Clermond Ferrand, , France

Research Site

Marseille, , France

Research Site

Montpellier, , France

Research Site

Nantes, , France

Research Site

Paris, , France

Research Site

Paris, , France

Research Site

Pierre-Bénite, , France

Research Site

Poitiers, , France

Research Site

Reims, , France

Research Site

Rennes, , France

Research Site

Toulouse, , France

Research Site

Vandœuvre-lès-Nancy, , France

Research Site

Athens, , Greece

Research Site

Bologna, , Italy

Research Site

Milan, , Italy

Research Site

Novara, , Italy

Research Site

Amsterdam, , Netherlands

Research Site

Utrecht, , Netherlands

Research Site

Salamanca, , Spain

Research Site

Bournemouth, , United Kingdom

Research Site

Leeds, , United Kingdom

Research Site

Leicester, , United Kingdom

Research Site

London, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Oxford, , United Kingdom

Research Site

Plymouth, , United Kingdom

Research Site

Southampton, , United Kingdom

Countries

United States; France; Greece; Italy; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39563886 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31866281 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Related Info

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Related Info

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SAP

Other Identifiers

2023-509356-34-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-003212-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACE-WM-001

Identifier Type: -

Identifier Source: org_study_id