An Open-label, Phase 2 Study of ACP-196 (Acalabrutinib) in Subjects With Mantle Cell Lymphoma

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

The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell Lymphoma (MCL).

Study Overview

• Status: Active, not recruiting
• Conditions: Mantle Cell Lymphoma (MCL)
• Intervention / Treatment: Drug: ACP-196 (acalabrutinib)

Detailed Description

This clinical trial is a Phase 2, multicenter, (approximately 70 global centers), open-label study in subjects with histologically documented MCL, who have relapsed after, or were refractory to, ≥ 1 (but not > 5) prior treatment regimens. Subjects will be enrolled and will take 100 mg of acalabrutinib twice per day (BID) in repeated 28-day cycles.

Treatment with acalabrutinib may be continued until disease progression or an unacceptable drug-related toxicity occurs. Dose modification provisions are provided in the study protocol.

All subjects will have hematology, chemistry, and urinalysis safety panels done at screening. Once dosing commences (Day 1), all subjects will be evaluated for safety, including serum chemistry and hematology, once weekly for the first 4 weeks, every 2 weeks in Cycle 2, every 4 weeks in Cycles 3 to 12, and every 24 weeks thereafter. PK/PD testing will be done in Cycles 1 and 2. Tumor assessments will be completed at 8- to 24-week intervals during the trial.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Monash, Australia
    • Research Site
  • Sydney, Australia, 2139
    • Research Site
  • Wodonga, Australia, 3690
    • Research Site
• Belgium
  • Brugge, Belgium, 8000
    • Research Site
  • Bruxelles, Belgium, 1200
    • Research Site
  • Bruxelles, Belgium, 1000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Czechia
  • Prague, Czechia, 100 34, CZ
    • Research Site
• France
  • Angers, France, 49033
    • Research Site
  • Caen, France, 14033
    • Research Site
  • Clermond Ferrand, France, 63003
    • Research Site
  • Creteil, France, 94010
    • Research Site
  • Dijon, France, 21000
    • Research Site
  • Grenoble Cedex 09, France, 38043
    • Research Site
  • La Roche - Sure-Yon, France, 85925
    • Research Site
  • Lille, France, 59000
    • Research Site
  • Montpellier, France, 34295
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Paris, France, 75015
    • Research Site
  • Paris cedex 13, France, 75651
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Pierre-Benite, France, 69310
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Rouen, France, 76038
    • Research Site
  • St Priest en Jarez, France, 42270
    • Research Site
  • Strasbourg Cedex, France, 67098
    • Research Site
  • Toulouse, France, 31100
    • Research Site
  • Tours, France, 37000
    • Research Site
  • Vandoeuvre-les-Nancy, France, 54500
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Novara, Italy, 28100
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Maastricht, Netherlands, 6202 AZ
    • Research Site
  • Rotterdam, Netherlands, 3062 PA
    • Research Site
• Poland
  • Kraków, Poland, 30-727
    • Research Site
  • Lodz, Poland, 93-510
    • Research Site
  • Olsztyn, Poland, 10-228
    • Research Site
• Spain
  • Badalona, Spain, 8916
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • Leicester, United Kingdom, LE1 7RH
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Oxford, United Kingdom, 0X3 7LE
    • Research Site
  • Plymouth, United Kingdom, PL6 8DH
    • Research Site
  • Southampton, United Kingdom, SO16 6YD
    • Research Site
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Niles, Illinois, United States, 60714
      • Research Site
    • Peoria, Illinois, United States, 61615
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 2215
      • Research Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Agreement to use 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.

Exclusion criteria:

• 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 (acalabrutinib), 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, or corrected QT interval (QTc) > 480 msec.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Breast feeding or pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACP-196 (acalabrutinib) Regimen 1	Drug: ACP-196 (acalabrutinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) of ACP-196 (Acalabrutinib) in Subjects With Previously Treated MCL.	The overall response rate (ORR) is defined as the proportion of subjects achieving either a partial remission (response) (PR) or complete response (CR) according to the Lugano Classification for NHL (Cheson 2014) as assessed by investigators, where SD stands for Stable Disease, PD for Progressive Disease and NE for Not Evaluable.	From the date of the first dose until 30 days after the last dose of the study drug or start of a new anti-cancer treatment, whichever came first, assessed up to approximately 4 year and 10 months. 1 cycle =28 days

Collaborators and Investigators

• Sponsor: Acerta Pharma BV
• Investigators: Study Director: Acerta Pharma, 1-888-292-9613

Publications and helpful links

General Publications

• Wang M, Rule S, Zinzani PL, Goy A, Casasnovas O, Smith SD, Damaj G, Doorduijn J, Lamy T, Morschhauser F, Panizo C, Shah B, Davies A, Eek R, Dupuis J, Jacobsen E, Kater AP, Le Gouill S, Oberic L, Robak T, Covey T, Dua R, Hamdy A, Huang X, Izumi R, Patel P, Rothbaum W, Slatter JG, Jurczak W. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018 Feb 17;391(10121):659-667. doi: 10.1016/S0140-6736(17)33108-2. Epub 2017 Dec 11.

Helpful Links

• redacted CSP
• redacted CSR Synopsis
• redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2015
• Primary Completion (Actual): December 4, 2020
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 11, 2014
• First Posted (Estimated): August 12, 2014

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: MCL; Mantle Cell Lymphoma; Bruton tyrosine kinase inhibitor; Btk; Acalabrutinib; ACP-196; ACE-LY-004; Calquence
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: ACE-LY-004; 2014-002117-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No