Clinical trial · Interventional
Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone for for Richter Syndrome Transformed From CLL
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 26, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260926-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Richter Syndrome | — | UNRESOLVED | — |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Liposomal mitoxantrone | Drug | — | UNRESOLVED |
| Lisaftoclax (APG-2575) | Drug | — | UNRESOLVED |
| Pirtobrutinib | Drug | Pirtobrutinib | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone
- description
- This regimen adopts a 21-day treatment cycle, for a total of 4 cycles. Upon completion of the 4-cycle treatment, patients who achieve remission based on efficacy assessment results may receive sequential CAR-T therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- interventionNames
- Drug: Lisaftoclax (APG-2575)
- Drug: Rituximab
- Drug: Pirtobrutinib
- Drug: Liposomal mitoxantrone
Primary outcomes (1)
- measure
- CR rate
- timeFrame
- At the end of 4 cycles (each cycle is 21 days) of induction therapy
Secondary outcomes (5)
- measure
- ORR
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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).
References
Publications (0)
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