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NCT07831395

PHASE2

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

Sponsor: Institute of Hematology & Blood Diseases Hospital, China

View on ClinicalTrials.gov

Summary

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.

Official title: 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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-09-01

Completion Date

2031-12-31

Last Updated

2026-09-21

Healthy Volunteers

Conditions

Richter Syndrome

Interventions

DRUG

Lisaftoclax (APG-2575)

Lisaftoclax oral with mandatory 6-day dose ramp-up (20mg→50mg→100mg→200mg→400mg→600mg QD), maintained at 600mg QD Days 1-21; standardized tumor lysis syndrome (TLS) prophylaxis (hydration + urate-lowering agents) and intensive serial TLS lab monitoring during dose escalation

DRUG

Rituximab

Rituximab 375 mg/m² IV infusion on Cycle Day 0; premedication with paracetamol, diphenhydramine and corticosteroids for infusion reaction prophylaxis

DRUG

Pirtobrutinib

Pirtobrutinib 200 mg oral QD, Days 1-21 of each cycle

DRUG

Liposomal mitoxantrone

Liposomal mitoxantrone 18 mg/m² IV infusion on Cycle Day 1

Inclusion Criteria: Inclusion Criteria 1. Age ≥ 18 years, any gender. 2. Histopathologically confirmed clonally related Chronic Lymphocytic Leukemia (CLL)-derived Richter Syndrome (RS) with diffuse large B-cell lymphoma (DLBCL) transformation. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2. 4. Estimated survival ≥ 3 months. 5. Adequate organ function as defined below: 1. Hematologic: Absolute Neutrophil Count (ANC) ≥ 1.0 × 10⁹/L; Platelet (PLT) ≥ 30 × 10⁹/L. Cytopenias secondary to CLL bone marrow infiltration are acceptable. 2. 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. 3. Renal: estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min. 6. Voluntarily provides written informed consent prior to any study-related procedures. 7. Able to take oral study medications, communicate with investigators, and complete all scheduled study assessments and follow-up visits. 8. Willing and able to comply with all protocol-specified restrictions and prohibitions. Exclusion Criteria: 1. RS transformation to histologic subtypes other than DLBCL (e.g., Hodgkin lymphoma, Burkitt lymphoma). 2. Non-CLL clonal DLBCL transformation confirmed via Immunoglobulin Heavy Chain Variable (IgHV) sequencing analysis. 3. Central Nervous System (CNS) lymphoma involvement (lymphoma cells detected in cerebrospinal fluid or intracranial lesions identified on brain MRI/CT). 4. Prior treatment with pirtobrutinib or lisaftoclax. 5. Prior chimeric antigen receptor T-cell (CAR-T) therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). 6. Uncontrolled active infection requiring intravenous antibiotic therapy. 7. 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. 8. Requirement for concurrent warfarin or other vitamin K antagonist anticoagulation; concurrent treatment with strong CYP3A4/5 inhibitors. 9. Medical history of stroke, intracranial hemorrhage, or other severe bleeding events. 10. Severe hepatic or renal impairment failing to meet the organ function thresholds listed in inclusion criteria. 11. Known hypersensitivity to any component of the study regimen. 12. Pregnant or breastfeeding female patients. 13. Psychiatric disorder or cognitive impairment precluding adherence to study procedures. 14. Any other condition deemed inappropriate for trial participation by the investigator (e.g., substance abuse, unresolved legal issues).

Locations (6)

Henan Cancer Hospital

Zhengzhou, Henan, China

The second Xiangya hospital of central south university

Changsha, Hunan, China

The First affiliated hospital of Nanchang University

Nanchang, Jiangxi, China

Nanfang Hospital Southern Medical University

Guangzhou, China

Jiangsu Province Hospital

Nanjing, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (6)