Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone for for Richter Syndrome Transformed From CLL

Trial details

Who runs it

Institute of Hematology & Blood Diseases Hospital, China

Trial code

NCT07831395

Record updated

21 September 2026

Original description

This single-arm, multicenter, open-label phase II trial evaluates the efficacy and safety of rituximab + pirtobrutinib + lisaftoclax + liposomal mitoxantrone in adults with CLL-transformed Richter syndrome (CLL-RS). All eligible patients receive 4 cycles (21 days each) of the quadruple regimen: rituximab 375 mg/m² IV on Day 0, pirtobrutinib 200 mg PO daily (D1-21), lisaftoclax ramp-up to 600 mg QD (D1-21), and liposomal mitoxantrone 18 mg/m² IV on D1, with TLS prophylaxis/monitoring. Primary endpoint: CR rate after 4 cycles. Secondary endpoints: ORR, DOR, PFS, OS, MRD negativity, and safety. Post-induction: CR/PR patients proceed to allo-HSCT, CAR-T, or maintenance; SD/PD receive alternative/palliative care. Long-term follow-up starts after discontinuation.Read full original descriptionShow less

Single-Arm, Multicenter, Prospective Phase II Clinical Study of Rituximab Combined With Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone for Richter Syndrome Transformed From Chronic Lymphocytic Leukemia

This single-arm, multicenter, open-label phase II trial evaluates the efficacy and safety of rituximab + pirtobrutinib + lisaftoclax + liposomal mitoxantrone in adults with CLL-transformed Richter syndrome (CLL-RS). All eligible patients receive 4 cycles (21 days each) of the quadruple regimen: rituximab 375 mg/m² IV on Day 0, pirtobrutinib 200 mg PO daily (D1-21), lisaftoclax ramp-up to 600 mg QD (D1-21), and liposomal mitoxantrone 18 mg/m² IV on D1, with TLS prophylaxis/monitoring. Primary endpoint: CR rate after 4 cycles. Secondary endpoints: ORR, DOR, PFS, OS, MRD negativity, and safety. Post-induction: CR/PR patients proceed to allo-HSCT, CAR-T, or maintenance; SD/PD receive alternative/palliative care. Long-term follow-up starts after discontinuation.

Inclusion: Age ≥ 18 years, any gender; Histopathologically confirmed clonally related Chronic Lymphocytic Leukemia (CLL)-derived Richter Syndrome (RS) with diffuse large B-cell lymphoma (DLBCL) transformation; Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2; Estimated survival ≥ 3 months; Adequate organ function as defined below:; Hematologic: Absolute Neutrophil Count (ANC) ≥ 1.0 × 10⁹/L; Platelet (PLT) ≥ 30 × 10⁹/L. Cytopenias secondary to CLL bone marrow infiltration are acceptable; Hepatic: Total bilirubin ≤ 2.0 × Upper Limit of Normal (ULN); ≤ 3.0 × ULN for patients with CLL liver involvement or Gilbert syndrome. Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤ 2.5 × ULN; ≤ 5.0 × ULN for patients with CLL liver infiltration; Renal: estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min; Voluntarily provides written informed consent prior to any study-related procedures; Able to take oral study medications, communicate with investigators, and complete all scheduled study assessments and follow-up visits; Willing and able to comply with all protocol-specified restrictions and prohibitions.

Exclusion: Prior treatment with pirtobrutinib or lisaftoclax; Prior chimeric antigen receptor T-cell (CAR-T) therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT); Requirement for concurrent warfarin or other vitamin K antagonist anticoagulation; concurrent treatment with strong CYP3A4/5 inhibitors; Uncontrolled active infection requiring intravenous antibiotic therapy; Severe cardiopulmonary disease: uncontrolled hypertension (systolic BP ≥ 180 mmHg or diastolic BP ≥ 110 mmHg), unstable angina, myocardial infarction or cerebral infarction within the past 6 months; Medical history of stroke, intracranial hemorrhage, or other severe bleeding events; Severe hepatic or renal impairment failing to meet the organ function thresholds listed in inclusion criteria; Known hypersensitivity to any component of the study regimen; Psychiatric disorder or cognitive impairment precluding adherence to study procedures; Any other condition deemed inappropriate for trial participation by the investigator (e.g., substance abuse, unresolved legal issues); RS transformation to histologic subtypes other than DLBCL (e.g., Hodgkin lymphoma, Burkitt lymphoma); Non-CLL clonal DLBCL transformation confirmed via Immunoglobulin Heavy Chain Variable (IgHV) sequencing analysis; Central Nervous System (CNS) lymphoma involvement (lymphoma cells detected in cerebrospinal fluid or intracranial lesions identified on brain MRI/CT); Pregnant or breastfeeding female patients.

ClinicalTrials.gov NCT07831395