A Trial to See the Effects of ACP-196 (the test drug) in Patients who have Mantle Cell Lymphoma

• Register: EUCTR
• Last refreshed on: 12 December 2023
• Main ID: EUCTR2014-002117-28-NL
• Date of registration: 15/04/2015
• Prospective Registration: Yes
• Primary sponsor: Acerta Pharma BV
• Public title: A Trial to See the Effects of ACP-196 (the test drug) in Patients who have Mantle Cell Lymphoma
• Scientific title: An Open-label, Phase 2 Study of ACP-196 in Subjects with Mantle Cell Lymphoma
• Date of first enrolment: 15/04/2015
• Target sample size: 117
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002117-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Czech Republic, Czechia, Denmark, France, Germany, Italy, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom, United States

Contacts

• Name: ACE-LY-004 Clincial Team
• Affiliation: Acerta Pharma BV

• Name: ACE-LY-004 Clincial Team
• Affiliation: Acerta Pharma BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men and women = 18 years of age.
2. Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
3. Disease has relapsed after or been refractory to = 1 prior therapy for MCL and now requires further treatment.
4. Documented failure to achieve at least PR with, or documented disease progression after, the most recent treatment regimen.
5. 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).
6. At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects having received = 2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.)
7. Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
8. Agreement to use acceptable methods of contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.
9. Agreement to refrain from sperm donation during the study and for 30 days after the last dose of study drug.
10. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
11. 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).
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

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 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 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 inhibitors, phosphoinositide-3 kinase (PI3K), or PI3KSyk 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 28 days of first dose of study drug
16 Requires treatment with long-acting proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole)
17 ANC < 0.5 75 x 109/L or platelet count < 25 50 x 109/L unless due to; 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 (unless due to Gilbert’s disease); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 3.0 x ULN unless disease related.
19. Breastfeeding or pregnant.
20. Concurrent participation in another therapeutic clinical trial.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mantle Cell Lymphoma
MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: ACP-196
Pharmaceutical Form: Capsule
INN or Proposed INN: not yet assigned
Current Sponsor code: ACP-196
Other descriptive name: ACP-196
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): The primary endpoint of the study is the overall response rate (ORR) defined as a subject achieving either a partial remission (PR) or complete remission (CR) response according to the Lugano Classification for non-Hodgkin lymphoma as assessed by investigators.

Timepoint(s) of evaluation of this end point: @ 30 days after stopping study treatment

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 Objective: • To characterize the safety profile of ACP-196
• To characterize the pharmacokinetic (PK) profile of ACP-196
• To evaluate the PD effects of ACP-196

Secondary Outcome(s)

Secondary end point(s): Efficacy:
• duration of response (DOR)
• progression-free survival (PFS)
• overall survival (OS)

Safety:
• frequency, severity, and relatedness of adverse events
• frequency of adverse events requiring discontinuation of study drug or dose reductions
• effect of ACP-196 on peripheral T/B/NK cell counts
• effect of ACP-196 on serum immunoglobulin levels

Pharmacokinetics:
• plasma pharmacokinetics of ACP-196

Patient Reported Outcomes (PRO):
• health-related quality of life

Pharmacokinetics:
• plasma pharmacokinetics of ACP-196

Patient Reported Outcomes (PRO):
• health-related quality of life

Timepoint(s) of evaluation of this end point: @ 30 days after stopping study treatment

Secondary ID(s)

118717

2014-002117-28-GB

ACE-LY-004

Source(s) of Monetary Support

Acerta Pharma BV

Ethics review

Status: Approved
Approval date: 13/04/2015
Contact: