NCT02180724 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-06-16

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Progression-free Survival (PFS) of Acalabrutinib by Investigator

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outcome · POSTED

Overall Survival (OS) of Acalabrutinib by Investigator

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outcome · POSTED

Summary of Duration of Response (DOR)

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Subjects previously treated with Waldenström Macroglobulinemia N=92
intervention Names
Drug: Acalabrutinib (ACP-196)
label
Previously Treated
type
EXPERIMENTAL
description
Subjects with treatment-naïve Waldenström Macroglobulinemia. N=14
intervention Names
Drug: Acalabrutinib (ACP-196)
label
Treatment Naïve
type
EXPERIMENTAL

interventions

arm Group Labels
Previously Treated
name
Acalabrutinib (ACP-196)
other Names
Acalabrutinib
type
DRUG
arm Group Labels
Treatment Naïve
name
Acalabrutinib (ACP-196)
other Names
Acalabrutinib
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 107
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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).
description
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.
measure
Overall Response Rate (ORR) of Acalabrutinib in Subjects as Assessed by Investigator Per IWWM 3rd Criteria
time Frame
Up to approximately 3.8 years. Data cut at when last patient has completed Cycle 27 (28 days per Cycle).

secondary Outcomes

description
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.
measure
Progression-free Survival (PFS) of Acalabrutinib by Investigator
time Frame
Up to approximately 3.8 years. Data cut at last subject have completed Cycle 27 (28 days per Cycle).
description
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.
measure
Overall Survival (OS) of Acalabrutinib by Investigator
time Frame
Primary analysis occur when all subjects have completed Cycle 27 or have discontinued before Cycle 27.
description
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.
measure
Summary of Duration of Response (DOR)
time Frame
Primary analysis occur when all subjects have completed Cycle 27 or have exit the study

Full study description

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.

Source references

references

citation
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.
pmid
41985004
type
DERIVED
citation
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
type
DERIVED
citation
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
type
DERIVED