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

NCT02180724 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: ACE-WM-0012023-509356-34-002014-003212-36
• Study Type: interventional
• Target: 107
• Locations: 7 countries
• Sites: 38

Brief Summary

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)

Keywords

Bruton tyrosine kinase inhibitor; Btk; Waldenström Macroglobulinemia; WM; Waldenström; Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (3)

• Progression-free Survival (PFS) of Acalabrutinib by Investigator

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

• Overall Survival (OS) of Acalabrutinib by Investigator

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

• Summary of Duration of Response (DOR)

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

Study Arms (2)

Previously Treated

EXPERIMENTAL

Subjects previously treated with Waldenström Macroglobulinemia N=92

Drug: Acalabrutinib (ACP-196)

Treatment Naïve

EXPERIMENTAL

Subjects with treatment-naïve Waldenström Macroglobulinemia. N=14

Drug: Acalabrutinib (ACP-196)

Interventions

Acalabrutinib (ACP-196) DRUG

Also known as: Acalabrutinib

Previously Treated

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (38)

Research Site

Santa Barbara, California, 93105, United States

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Aurora, Colorado, 80012, United States

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Washington D.C., District of Columbia, 20007, United States

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Minneapolis, Minnesota, 55404, United States

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New York, New York, 10021, United States

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Nashville, Tennessee, 37203, United States

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Austin, Texas, 78705, United States

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Bedford, Texas, 76022, United States

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Houston, Texas, 77030, United States

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Vancouver, Washington, 98684, United States

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Aurillac, 15002, France

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Clermond Ferrand, 63003, France

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Marseille, 13273, France

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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75015, France

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Paris, 75651, France

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Pierre-Bénite, 69495, France

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Poitiers, 86021, France

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Reims, 51092, France

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Rennes, 35000, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54500, France

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Athens, 11528, Greece

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Bologna, 40138, Italy

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Milan, 20162, Italy

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Novara, 28100, Italy

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Amsterdam, 1105AZ, Netherlands

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Utrecht, 2508GA, Netherlands

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Salamanca, 37007, Spain

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Bournemouth, BH7 7DW, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Leicester, LE1 7RH, United Kingdom

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London, NW1 2BU, United Kingdom

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London, SW3 6JJ, United Kingdom

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Oxford, OX3 7LE, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39563886 DERIVED

• 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.

  PMID: 31866281 DERIVED

Related Links

• Related Info
• Related Info
• SAP

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: Acerta Pharma

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca Clinical study Information Center

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2014
• First Posted: July 3, 2014
• Study Start: September 11, 2014
• Primary Completion: October 1, 2019
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 20, 2026
• Results First Posted: April 24, 2020

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

NL (2); ES (1); GR (1); GB (8); IT (3); FR (13); US (10)