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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acerta Pharma B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jun 2015 → 3 Nov 2025

Decision date (initial)

2024-06-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Acerta Pharma BV

External identifiers

EU CT number

2023-509352-34-00

EudraCT number

2014-002117-28

ClinicalTrials.gov

NCT02213926

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Therapy, Dose response, Safety

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 objectives 3

1. To characterize the safety profile of acalabrutinib
2. To characterize the pharmacokinetic (PK) profile of acalabrutinib
3. To evaluate the PD effects of acalabrutinib

Conditions and MedDRA coding

Mantle Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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.
9. 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 or tablets 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).

Exclusion criteria 23

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 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). Note: this criterion no longer applies to patients who have switched from acalabrutinib capsules to tablets.
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 CYP3A inhibitor/inducer.
23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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) according to the Lugano Classification for NHL as assessed by investigators.

Secondary endpoints 3

1. Efficacy: • duration of response (DOR) • progression-free survival (PFS) • overall survival (OS) • IRC-assessed ORR, DOR and PFS per Lugano Classification
2. 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
3. Pharmacokinetics: • plasma pharmacokinetics of acalabrutinib

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acerta Pharma B.V.

Sponsor organisation

Acerta Pharma B.V.

Address

Kloosterstraat 9

City

Oss

Postcode

5349 AB

Country

Netherlands

Scientific contact point

Organisation

Acerta Pharma B.V.

Contact name

Global Clinical Lead

Public contact point

Organisation

Acerta Pharma B.V.

Contact name

Global Clinical Lead

Third parties 3

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications