Zanubrutinib Plus Lenalidomide for Frail Elderly Patients With Newly Diagnosed PCNSL
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age70+
SponsorXiaohui Ren
About this trial
This is a prospective, single-arm, phase II clinical study evaluating the efficacy and safety of Zanubrutinib (a BTK inhibitor) plus Lenalidomide (an immunomodulatory drug) in frail elderly patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The study plans to enroll 33 patients who are aged ≥ 70 years and classified as frail, a population for whom standard first-line treatment regimens, high-dose methotrexate-based chemotherapy, may be "unfit". This study includes screening phase, induction phase, consolidation phase and maintenance phase. The screening period is defined as within 1 week prior to the first dose. During induction, participants will receive Zanubrutinib 160 mg orally twice daily continuously and Lenalidomide 25 mg orally once daily on days 1-21 of each 28-day cycle for three cycles. Participants who achieve a partial response (PR) or complete response (CR) after induction will receive three additional 28-day consolidation cycles of the same regimen. Participants who achieve a CR after consolidation will continue maintenance treatment with Zanubrutinib and Lenalidomide until disease progression. Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria and assessed every 3 months. The primary endpoint is the complete response rate (CRR) at the end of induction therapy. Secondary endpoints include overall response rate (ORR) at the end of induction therapy, CRR and ORR at the end of consolidation therapy, One-year and two-year progression-free survival (PFS) rates, Duration of response (DOR), overall survival (OS), adverse event (AE) and serious adverse event (SAE). Exploratory liquid-biopsy analyses will be performed to evaluate treatment response and prognosis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 70 years.
IADL ≤ 5 residual functions, or
CIRS: ≥ 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2, or
Age ≥ 80 years with "UNFIT" profile "UNFIT" profile: ADL = 5 residual functions or IADL = 6-7 residual functions, or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2.
Disqualifiers
Any disease or condition that may impair drug absorption (e.g., active inflammatory gastrointestinal disease, active gastric ulcer, chronic diarrhea, dysphagia, prior gastrectomy, gastroparesis, or short bowel syndrome).
Known hypersensitivity to zanubrutinib, lenalidomide, or any excipient contained in either drug.
Active bleeding within 1 month before treatment; a need for therapeutic anticoagulation during the study (e.g., warfarin or other vitamin K antagonists); or any condition associated with an increased risk of bleeding or coagulopathy (e.g., high-risk esophageal varices or active ulcer disease).
High risk of thrombosis.
Trial design
Design model
Single group
Treatments tested in this trial
Zanubrutinib
DrugZanubrutinib will be administered orally at 160 mg twice daily. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment.
Lenalidomide
DrugLenalidomide will be administered orally at 25 mg once daily on days 1-21 of each cycle. Each treatment cycle will last 28 days. Induction phase: Induction treatment will consist of three cycles. Consolidation phase: Patients who achieve a partial response (PR) or complete response (CR) after induction treatment will proceed to consolidation treatment. Consolidation treatment will consist of three cycles. Maintenance phase: Patients who achieve a CR after consolidation will proceed to maintenance treatment.
Treatment groups
33 Participants
are divided into 1 treatment groupGroup A: Zanubrutinib plus lenalidomideExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
CRR
complete response rate
Time frame
From the first day of treatment to the completion of induction treatment (3 months)Secondary outcomes
1
CRR
complete response rate
Time frame
From the first day of treatment to the completion of consolidation treatment (6 months)2
ORR
overall response rate
Time frame
From the first day of treatment to the completion of induction treatment (3 months)3
ORR
overall response rate
Time frame
From the first day of treatment to the completion of consolidation treatment (6 months)4
PFS
progression-free survival
Time frame
1-year and 2-year PFS rates, and the time interval from the start of treatment to tumor progression or death from any cause (up to 24 months).Other outcomes
1
CSF/PLA ctDNA and cfRNA
Changes in cerebrospinal fluid and plasma ctDNA and cfRNA
Time frame
From baseline through the end of induction and consolidation treatment, during maintenance treatment, and at disease progression (up to 24 months).2
Change From Baseline in EORTC QLQ-C30 Scale Scores
Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, version 3.0 (EORTC QLQ-C30). The questionnaire generates a global health status/quality-of-life score, five functional scale scores (physical, role, emotional, cognitive, and social functioning), three symptom scale scores (fatigue, nausea/vomiting, and pain), and six single-item scores (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each scale or item score is linearly transformed to a range of 0 to 100 according to the EORTC scoring manual. Higher scores on the functional scales and global health status/quality-of-life scale indicate better functioning or quality of life, whereas higher scores on the symptom scales and single-item measures indicate greater symptom burden or problems. Change from baseline is calculated as the post-baseline score minus the baseline score.
Time frame
Baseline; end of Cycle 3 (approximately Week 12); end of Cycle 6 (approximately Week 24); and every 3 months thereafter until disease progression or treatment discontinuation, up to 24 months3
Change From Baseline in EORTC QLQ-BN20 Scale and Single-Item Scores
Brain tumor-related symptoms and problems will be assessed using the 20-item European Organisation for Research and Treatment of Cancer Brain Neoplasm Module (EORTC QLQ-BN20), administered together with the EORTC QLQ-C30. The instrument generates four multi-item scale scores (future uncertainty, visual disorder, motor dysfunction, and communication deficit) and seven single-item scores (headache, seizures, drowsiness, hair loss, itchy skin, weakness of the legs, and bladder control). Each score is linearly transformed to a range of 0 to 100 according to the EORTC scoring manual. Higher scores indicate greater symptom burden or more severe problems. Change from baseline is calculated as the post-baseline score minus the baseline score.
Time frame
Baseline; end of Cycle 3 (approximately Week 12); end of Cycle 6 (approximately Week 24); and every 3 months thereafter until disease progression or treatment discontinuation, up to 24 months4
Change From Baseline in Mini-Mental State Examination Total Score
Global cognitive function will be assessed using the Mini-Mental State Examination (MMSE). The MMSE evaluates orientation, registration, attention and calculation, recall, language, and visuospatial construction. The total score ranges from 0 to 30, with higher scores indicating better cognitive function and lower scores indicating greater cognitive impairment. Change from baseline is calculated as the post-baseline total score minus the baseline total score.
Time frame
Baseline; end of Cycle 3 (approximately Week 12); end of Cycle 6 (approximately Week 24); and every 3 months thereafter until disease progression or treatment discontinuation, up to 24 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Xiaohui Ren
Lead sponsor
Beijing Tiantan Hospital
Sponsor institution
Source ClinicalTrials.gov