Central Nervous System Lymphoma
Conditions
Keywords
CNS Lymphoma
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.
Detailed description
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.
Interventions
DRUGAcalabrutinib
Acalabrutinib at 100 mg is taken orally approximately every 12 hours until disease progression or unacceptable toxicity.
Sponsors
UNC Lineberger Comprehensive Cancer Center
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Simon Two-stage study to a pilot study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 2 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | up to 3 years | All treatment-attributed adverse events and toxicities will be assessed, classified, and graded in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. |
| Number of Different Types of Toxicity | up to 3 years | All treatment-attributed adverse events and toxicities will be assessed, classified, and graded in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting and a grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE |
| Progression-free Survival (PFS) | Up to 400 days (Median 62 days ) | Progression-free survival (PFS) is defined from the date of initiating study treatment to the date of disease progression per the International Primary CNS Lymphoma Collaborative Group response assessment criteria or death as a result of any cause. Categories included complete response (no evidence of disease), partial response (reduction in disease burden), stable disease (no significant change), and progressive disease (disease worsening), based on radiographic findings, corticosteroid use, and clinical status. |
| Complete Response (CR) Rate | 2 years | Complete Response (CR) is defined using the International Primary CNS Lymphoma Collaborative Group response assessment criteria for primary CNS lymphoma. |
| Duration of Response (DoR) | 2 years | Duration of response (DoR) is defined as time from documentation of tumor response to disease progression according to the International Primary CNS Lymphoma Collaborative Group response assessment criteria. |
| Overall Survival (OS) | Up to 600 days (median 203.5 days) | OS will be measured from the date of initiating study treatment to the date of death or 5 years (whichever is first). Subjects who have not died by the analysis data cut-off date will be censored at their last date of contact. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORChristopher Dittus
UNC Lineberger Comprehensive Cancer Center
Participant flow
Pre-assignment details
Ten eligible participants received study treatment between 10/15/2020 and 5/6/2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 5 / 10 |
Outcome results
None listed