Mantle Cell Lymphoma MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Product Code: ACP-196
Pharmaceutical Form: Capsule
INN or Proposed INN: acalabrutinib
Current Sponsor code: ACP-196
Other descriptive name: ACP-196
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
Acerta Pharma B.V.
Eligibility
Sex/Gender
All
Inclusion 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 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 inhibitor-exposed.) 7. Eastern Cooperative Oncology Group (ECOG) performance status of = 2. 8. 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 study drug. 09. This criterion has been removed as of protocol amendment 8. 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 patient privacy regulations). Are the trial subjects under 18? no Number of subjects for this age range: 0 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
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 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 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 CYP3A inhibitor/inducer. 23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months prior
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the activity of acalabrutinib in subjects with relapsed/refractory (R/R) MCL as measured primarily by response rate. In addition, activity of acalabrutinib will be assessed by duration of response, progression-free survival, and overall survival.;Secondary Objective: • To characterize the safety profile of acalabrutinib • To characterize the pharmacokinetic (PK) profile of acalabrutinib • To evaluate the PD effects of acalabrutinib;Primary end point(s): The primary endpoint of the study is the overall response rate (ORR) defined as the proportion of subjects achieving either a partial response (PR) or complete response (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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • duration of response (DOR) • progression-free survival (PFS) • overall survival (OS) • IRC-assessed ORR, DOR and PFS per Lugano Classification Safety: • frequency and severity of adverse events • frequency of adverse events requiring discontinuation of study drug or dose reductions • effect of acalabrutinib on peripheral T/B/natural killer (NK) cell counts • effect of acalabrutinib on serum immunoglobulin levels Pharmacokinetics: • plasma pharmacokinetics of acalabrutinib Exploratory Endpoints: Patient Reported Outcomes (PRO): • health-related quality of life • Time to response (TRR) per Lugano Classification as assessed by investigators and IRC - time to initial response - time to best response - time to complete response •IRC-assessed ORR, DOR, TTR and PFS per Revised Response Criteria for Malignant Lymphoma;Timepoint(s) of evaluation of this end point: @ 30 days after stopping study treatment | — |
Countries
Australia, Belgium, Czech Republic, France, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactACE-LY-004 Clincial Team
Acerta Pharma B.V.
Outcome results
None listed