A Trial to See the Effects of ACP-196 (the test drug) in Patients who have Mantle Cell Lymphoma
- Conditions
- Mantle Cell LymphomaMedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002117-28-IT
- Lead Sponsor
- ACERTA PHARMA BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 117
• Men and women aged 18 years.
• Pathologically confirmed MCL, with documentation of monoclonal B cells
die have a chromosomal translocation t (11; 14) (q13; q32) and / or one
overexpression of cyclin Dl.
• Relapsing disease after, or refractory to, 1 previous therapy for [V1CL and now
requesting further treatment.
• Failure to document at least one RP with the regime of
recent pki treatment or progression of the disease documented after the regimen
of more recent treatment.
• Presence of lymphadenopathy or extranodal lymphoid malignancy
radiologically measurable (defined as the presence of 1 lesion that measures
2.0 cm in the longest dimension and 1.0 cm in the perpendicular dimension
long standing evaluated by computerized tomography [TC]).
• At least 1, but no more than 5, previous treatment regimens for MCL. (Note: I
subjects who received 2 dcli of previous treatment with bortezomib or
any other commercially available proteasome inhibitor, either as an agent
in monotherapy or as part of a combination therapeutic regimen, they will come
considered exposed to proteasome inhibitor).
Status of validity according to the Eastern Group of Cooperative Oncology (Eastern
Cooperative Oncology Group, ECOG) <2.
• Sexually active women who are able to conceive children must accept
use highly effective forms of contraception during the study and for 2 days
after the last dose of the study drug
• This criterion is removed as per protocol version 8Volontà and possibility of
participate in all assessments and procedures required by this protocol
study, including the ability to swallow the capsules without difficulty.
• Ability to understand the purpose and risks of the study and to provide a consensus
informed signed and dated and authorization to use health information
protected (in compliance with national and local regulations concerning the privacy of the
subject).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 58
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 ACP-196, 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 or corrected QT interval (QTc)> 480 msec.
4. 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.
5. Any immunotherapy within 4 weeks of first dose of study drug.
6. 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).
7. Prior exposure to a BCR inhibitor (eg, Btk, phosphoinositide- 3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (eg, ABT-199).
8. 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.
9. Grade = 2 toxicity (other than alopecia) continuing from prior
anticancer therapy including radiation.
10. 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.
11. Major surgery within 4 weeks before first dose of study drug.
12. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
13. Known history of a bleeding diathesis (eg, hemophilia, von Willebrand disease)
14. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon) within 7 days of first dose
of study drug.
16. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, exlansoprazole, 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 < 30 x 109/L.
18. Creatinine > 2.5 x institutional upper limit of normal (ULN); total bilirubin > 2.5 x ULN ; and aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 3.0 x ULN.
19. Breastfeeding or pregnant.
20. Concurrent participation in another therapeutic clinical trial.
21. Known central nervous system (CNS) lymphoma or leptomeningeal
disease.
22. Requires treatment with a strong CYP3A4 inhibitor/inducer.
23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3
months pr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): The primary endpoint of the study is the overall response rate (ORR),<br>defined as a subject achieving either a partial response (PR) or complete<br>response (CR) according to the Lugano Classification for NHL as<br>assessed by investigators.;Timepoint(s) of evaluation of this end point: @ 30 days after stopping study treatment;Secondary Objective: ¿ To characterize the safety profile of ACP-196<br>¿ To characterize the pharmacokinetic (PK) profile of ACP-196<br>¿ To evaluate the PD effects of ACP-196;Main Objective: To determine the activity of ACP-196 in subjects with relapsed or refractory MCL as measured primarily by response rate. In addition, activity of ACP-169 will be assessed by duration of response, progression-free survival, and overall survival.
- Secondary Outcome Measures
Name Time Method