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

Phase 2

Completed

Conditions: Waldenström Macroglobulinemia
mobus Waldenström
10025320

Registration Number: NL-OMON53142

Lead Sponsor: ACERTA PHARMA, BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 7

Inclusion Criteria

•Men and women >= 18 years of age.
• Previously treated cohort only: A confirmed diagnosis of WM, which has
relapsed after, or been refractory to >= 1 prior 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:
o Symptomatic hyperviscosity with an IgM >= 5,000 mg/dL
o Disease-related neuropathy
• Serum concentration of IgM, as measured by serum protein electrophoresis
(SPEP) and immunofixation electrophoresis (IFE), that exceeds the upper limits
of normal or measurable nodal WM (defined as the presence of >= 1 lymph node
that measures >= 2.0 cm in the longest diameter and >= 1.0 cm in the longest
perpendicular diameter).
• Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
• Agreement to use highly effective forms of contraception during the study and
for 90 days after the last dose of acalabrutinib. Highly effective forms of
contraception are defined in Section 3.7.4 .
• Agreement to refrain from sperm donation during the study and for 90 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).

Exclusion Criteria

• 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 corrected QT interval (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 (eg, BTK, phosphoinositide-3 kinase [PI3K],
or spleen tyrosine kinase [SYK] inhibitors) or B-cell lymphoma 2 (BCL-2)
inhibitor (eg, 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 human immunodeficiency virus (HIV) or active infection with
hepatitis C virus (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 (eg, 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
antagonist (eg, phenprocoumon) within 28 days of first dose of study drug.
• Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole)
• Absolute neutrophil count (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 < 30 x 109/L.
• Creatinine > 2.5 x institutional upper limit of normal (ULN); total bilirubin
> 2.5 x ULN; or aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) > 3.0 x ULN.
• Lactating or pregnant.
• Concurrent participation in another therapeutic clinical trial.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To determine the ORR of acalabrutinib in subjects with WM as assessed by<br /><br>investigators.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Objectives:<br /><br>• To determine the ORR of acalabrutinib by IRC<br /><br>• To determine the DOR of acalabrutinib by investigator and by IRC, respectively<br /><br>• To determine the progression-free survival (PFS) of acalabrutinib by<br /><br>investigator and by IRC, respectively<br /><br>• To determine the overall survival (OS) of acalabrutinib<br /><br>• To characterize the PK profile of acalabrutinib<br /><br>• To characterize the safety of acalabrutinib<br /><br>• To evaluate the effect of acalabrutinib in health-related quality of life<br /><br>Exploratory Objective:<br /><br>• To evaluate the PD effects of acalabrutinib</p><br>