A Pilot Study of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas

NCT04548648 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LCCC1841
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test whether giving acalabrutinib is safe and effective in controlling relapsed central nervous system (CNS) lymphoma. Currently, there are no FDA-approved treatments for relapsed CNS lymphoma. Although acalabrutinib has not been approved for the treatment of CNS lymphoma, it was approved for the treatment of another type of lymphoma (mantle cell), by the Food and Drug Administration (FDA). Acalabrutinib acts similar to another cancer drug called ibrutinib. lbrutinib was tested in several research trials for the management of CNS lymphomas, and the results were promising. Acalabrutinib and ibrutinib attack a similar target found in CNS lymphoma. Acalabrutinib may do a better job in attacking this target than ibrutinib. The study doctors will be looking to see if acalabrutinib can shrink cancer cells.

Conditions

Central Nervous System Lymphoma

Keywords

CNS Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  The overall response rate (ORR) will be assessed based on the International Primary CNS Lymphoma Collaborative Group Response assessment criteria. Responder = Partial Response + Complete Response). Complete response (CR) as complete disappearance of contrast enhancement on magnetic resonance imaging (MRI), no evidence of ocular lymphoma, negative cerebrospinal fluid (CSF) cytology, and discontinuation of corticosteroid use for at least 2 weeks prior to the evaluation of response. Unconfirmed CR (Cru) is used to characterize radiographic findings that fulfill the criteria for a CR, but the patient remains on corticosteroids, or MRI that continues to show small but persistent enhancing abnormalities possibly related to biopsy or surgery. Partial response (PR) is defined as a 50% decrease in enhancing tumor or residual disease on eye examinations, or persistent or suspicious CSF cytology.

  2 months

Secondary Outcomes (5)

• Number of different types of toxicities

  3 years

• Progression-free survival (PFS)

  5 years

• Complete response (CR) rate

  2 years

• Duration of response (DoR)

  2 years

• Overall Survival (OS)

  5 years

Study Arms (1)

Open-label, single-arm

OTHER

A multicenter open-label, single-arm, phase 2 study designed to investigate the antitumor effects of acalabrutinib in subjects with relapsed primary central nervous system lymphoma (PCNSL), and relapsed secondary CNS lymphoma (SCNSL) with no evidence of current systemic disease. Subjects will receive acalabrutinib at the dose of 100 mg every 12 hours.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Acalabrutinib at 100 mg is taken orally approximately every 12 hours until disease progression or unacceptable toxicity.

Also known as: ACP-196, CALQUENCE

Open-label, single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
• 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).
• Age ≥18 years at the time of consent.
• Subject has adequate performance status as defined by The Eastern Cooperative Oncology Group (ECOG) of ≤ 2
• Subject has histological confirmation of biopsy-proven central nervous system (CNS) lymphoma or magnetic resonance imaging (MRI) findings consistent with CNS lymphoma if biopsy is not possible (due to inaccessible location). Subjects with intra-ocular lymphoma will not be excluded as long as there is also parenchymal disease.
• Subject has B-cell Non-Hodgkin Lymphoma.
• Subject has no evidence of systemic involvement of lymphoma confirmed by computerized tomography (CT) or positron emission tomography (PET)-CT imaging within 28 days prior to first dosing in the study.
• Subject must have received at least one prior line of chemotherapy for primary or secondary CNS lymphoma.
• Subject has adequate organ function as demonstrated by: System Laboratory Value Hematological\* Absolute Neutrophil Count (ANC) ≥ 1 x 109/L Platelets ≥ 75 x 109/L Renal\* Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula (Appendix B) Hepatic\* Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level \>1.5 mg/dL if their conjugated bilirubin is \<1.5× ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN (in the absence of lupus anticoagulant)

You may not qualify if:

• Prior cancer treatment that was completed less than 14 days prior to Day 1 of study dosing or if subject has not recovered from all reversible acute toxic effects of the regimen to grade ≤1 or baseline.
• Prior brain radiotherapy under the following conditions:
• Whole-brain radiotherapy (WBRT) that was completed less than 28 days prior to Day 1 of study dosing
• Stereotactic radiosurgery (SRS) that was competed less than 14 days prior to Day 1 of study dosing.
• Currently participating in or has participated in a study of an investigational agent within 28 days of first dosing with study treatment.
• Subject is pregnant or breastfeeding.
• Subject has active cerebrospinal fluid (CSF) involvement that requires ongoing intrathecal chemotherapy
• Previous exposure to a Bruton Tyrosine Kinase (BTK) inhibitor.
• Subjects with severe hepatic insufficiency, as defined by Child-Pugh Score \> 6.
• Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy.
• Subject requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 14 days of first dose of study drug. Subjects requires or is taking direct oral anticoagulants within 7 days of first dose of study drug.
• Subject requires treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
• Subject is currently receiving any chemotherapy, anticancer immunotherapy.
• Subject has clinically significant cardiovascular disease such as ventricular dysfunction, symptomatic coronary artery disease, 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 (NYHA) Functional Classification at screening. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
• Subject has familial short QT syndrome.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (3)

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Wake Forest University,The Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Related Links

• University of North Carolina - Lineberger Comprehensive Cancer Center - Clinical Trials

MeSH Terms

Interventions

acalabrutinib

Study Officials

• Christopher Dittus

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon Two-stage study to a pilot study.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 14, 2020
• Study Start: October 15, 2020
• Primary Completion: May 14, 2025
• Study Completion (Estimated): March 14, 2030
• Last Updated: June 4, 2025

Record last verified: 2025-05

Locations

US (3)