An Open-label, Phase 2 Study of ACP-196 in Subjects with Mantle Cell Lymphoma

Phase 2

Completed

Conditions: 10025320
Mantle Cell Lymphoma
MCL

Registration Number: NL-OMON53032

Lead Sponsor: ACERTA PHARMA B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 17

Inclusion Criteria

• Men and women >= 18 years of age.
• Pathologically confirmed MCL, with documentation of
monoclonal B cells that have a chromosome translocation
t(11;14)(q13;q32) and/or overexpress cyclin D1.
• Disease has relapsed after or been refractory to >= 1 prior
therapy for MCL and now requires further treatment.
• Documented failure to achieve at least partial response (PR)
with, or documented disease progression after, the most recent
treatment regimen.
• Presence of radiographically measurable lymphadenopathy or
extranodal lymphoid malignancy (defined as the presence of
>= 1 lesion that measures >= 2.0 cm in the longest dimension and
>= 1.0 cm in the longest perpendicular dimension as assessed
by computed tomography [CT] scan).
• At least 1, but no more than 5, prior treatment regimens for
MCL (Note: Subjects having received >= 2 cycles of prior
treatment with bortezomib or any other commercially available proteasome
inhibitor, either as a single agent or as part of a combination therapy
regimen, will be considered to be
proteasome inhibotor-exposed.)
• Eastern Cooperative Oncology Group (ECOG) performance
status of <= 2.
• Agreement to use acceptable forms of contraception during the
study and for 30 days after the last dose of study drug if
sexually active and able to bear or beget children.
• Agreement to refrain from sperm donation during the study and
for 30 days after the last dose of study drug.
• 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 subject 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 Acerta Pharma
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 ACP-196, 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.
• Malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small
bowel, gastric bypass, symptomatic inflammatory bowel
disease, or partial or complete bowel obstruction.
• Any immunotherapy within 4 weeks of first dose of study drug.
• The time from the last dose of the most recent chemotherapy
or experimental therapy to the first dose of study drug is
< 5 times the half-life of the previously administered agent(s).
• Prior exposure to a BCR inhibitor (eg, Btk inhibitors or
phosphoinositide-3 kinase [PI3K] inhibitors).
• Ongoing immunosuppressive therapy, including systemic or
enteric corticosteroids for treatment of MCL 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 ACP-196.
• Uncontrolled autoimmune hemolytic anemia or idiopathic
thrombocytopenia purpura.
• History of stroke or intracranial hemorrhage within 6 months
before the first dose of ACP-196.
• Requires anticoagulation with warfarin or a vitamin K
antagonist.
• Absolute neutrophil count (ANC) < 0.5 x 109/L or platelet count
< 25 x 109/L unless due to disease involvement in the bone
marrow.
• Creatinine > 2.5 x institutional upper limit of normal (ULN); total
bilirubin > 2.5 x ULN (unless due to Gilbert*s disease); and
aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) > 2.5 x ULN unless disease related.
• Significant screening electrocardiogram (ECG) abnormalities
including atrial fibrillation, 2nd-degree AV block type II, 3rddegree
AV block, Grade >= 2 bradycardia, or QTc > 480 msec.
• Breastfeeding 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 activity of acalabrutinib in subjects with relapsed/reractory<br /><br>(R/R) MCL as measured primarily by response rate. In addition, activity of<br /><br>acalabrutinib will be assessed by duration of response, progression-free<br /><br>survival and overall survival. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* To characterize the safety profile of acalabrutinib<br /><br>* To characterize the pharmacokinetic (PK) profile of acalabrutinib<br /><br>* To evaluate the PD effects of acalabrutinib</p><br>