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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty. 2. 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). 3. Age ≥18 years at the time of consent. 4. Subject has adequate performance status as defined by The Eastern Cooperative Oncology Group (ECOG) of ≤ 2. 5. 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. 6. Subject has B-cell Non-Hodgkin Lymphoma. 7. 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. 8. Subject must have received at least one prior line of chemotherapy for primary or secondary CNS lymphoma. 9. 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)

Exclusion Criteria:

Subjects meeting any of the following exclusion criteria will not be able to participate in this study. 1. 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. 2. 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.
3. Currently participating in or has participated in a study of an investigational agent within 28 days of first dosing with study treatment. 4. Subject is pregnant or breastfeeding. 5. Subject has active cerebrospinal fluid (CSF) involvement that requires ongoing intrathecal chemotherapy. 6. Previous exposure to a Bruton Tyrosine Kinase (BTK) inhibitor. 7. Subjects with severe hepatic insufficiency, as defined by Child-Pugh Score > 6. 8. Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy. 9. 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. 10. 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. 11. Subject is currently receiving any chemotherapy, anticancer immunotherapy. 12. 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. 13. Subject has familial short QT syndrome. 14. Subject has a history of malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass that is likely to affect absorption. 15. Subject has a known history of infection with HIV or any uncontrolled active significant infection. 16. Subject has a known history of drug-specific hypersensitivity or anaphylaxis to acalabrutinib (including active ingredient or excipient components). 17. Subject has active bleeding or history of bleeding diathesis. 18. Subject has a history of uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP). 19. Subject has a history of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of acalabrutinib. 20. Subject had major surgical procedure within 28 days of first dose of acalabrutinib. 21. Subject who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Subjects who are core antibody positive and viral load negative must receive entecavir Those who are HbsAg-positive, or hepatitis B PCR positive will be excluded. 22. Subjects who are hepatitis C antibody positive must have a negative polymerase chain reaction (PCR) result. Those who are hepatitis C PCR positive will be excluded. 23. Subjects with evidence of disease that investigator decides that is not suitable to enroll in the study. 24. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML). 25. Received a live virus vaccination within 28 days of first dose of study drug. 26. Any active significant infection. 27. Concurrent participation in another therapeutic clinical trial. 28. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04548648
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

UNC Lineberger Comprehensive Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Christopher Dittus
Principal Investigator Affiliation UNC Lineberger Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Central Nervous System Lymphoma
Study Website: View Trial Website
Additional Details

This multicenter open-label, single-arm, pilot study explores a safe and effective treatment for relapsed central nervous system lymphoma. The study investigates the antitumor effects and safety of acalabrutinib in subjects with relapsed primary central nervous system lymphoma (PCNSL) or relapsed secondary CNS lymphoma (SCNSL) with no evidence of current systemic disease. Types of SCNSL included in the study are: Diffuse large B-cell lymphoma, mantle cell lymphoma, plasmablastic lymphoma, and lymphoplasmacytic lymphoma. Up to 16 subjects will be enrolled to attain a total of 15 evaluable subjects. Duration of Follow-up All subjects will be followed for survival for 5 years or until death, whichever occurs first.

Arms & Interventions

Arms

Other: Open-label, single-arm

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.

Interventions

Drug: - Acalabrutinib

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Moffit Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffit Cancer Center

Tampa, Florida, 33612

Site Contact

Sameh Gaballa, MD

[email protected]

813-745-7223

Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina

Status

Recruiting

Address

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

Site Contact

Christopher Dittus

[email protected]

919-966-4431

Winston-Salem, North Carolina

Status

Recruiting

Address

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

Winston-Salem, North Carolina, 27157-1096

Site Contact

Cindy Miller

[email protected]

336-713-6770

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