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

NCT07831395 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026081
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Richter Syndrome

Keywords

Richter Syndrome; Lisaftoclax; Rituximab; Pirtobrutinib; liposomal mitoxantrone

Outcome Measures

Primary Outcomes (1)

• CR rate

  At the end of 4 cycles (each cycle is 21 days) of induction therapy

Secondary Outcomes (5)

• ORR

  At the end of 4-cycle(each cycle is 21 days) induction treatment period

• DOR

  From the date of first confirmed CR or PR until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years.

• PFS

  Up to 5 years

• OS

  Up to 5 years

• MRD Negative Rate

  At the end of 4 cycles (each cycle is 21 days) of induction therapy

Study Arms (1)

Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone

EXPERIMENTAL

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).

Drug: Lisaftoclax (APG-2575); Drug: Rituximab; Drug: Pirtobrutinib; Drug: Liposomal mitoxantrone

Interventions

Lisaftoclax (APG-2575) DRUG

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

Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone

Rituximab DRUG

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

Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone

Pirtobrutinib DRUG

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

Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone

Liposomal mitoxantrone DRUG

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

Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal Mitoxantrone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Prior treatment with pirtobrutinib or lisaftoclax.
• Prior chimeric antigen receptor T-cell (CAR-T) therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• 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.
• Requirement for concurrent warfarin or other vitamin K antagonist anticoagulation; concurrent treatment with strong CYP3A4/5 inhibitors.
• Medical history of stroke, intracranial hemorrhage, or other severe bleeding events.
• Known hypersensitivity to any component of the study regimen.
• Pregnant or breastfeeding female patients.
• 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).

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (6)

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

The second Xiangya hospital of central south university

Changsha, Hunan, 410012, China

Location

The First affiliated hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Nanfang Hospital Southern Medical University

Guangzhou, China

Location

Jiangsu Province Hospital

Nanjing, China

Location

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

Wuhan, China

Location

MeSH Terms

Interventions

Lisaftoclax; Rituximab; pirtobrutinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Tingyu Wang

CONTACT

+86 15692201678; wangtingyu@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: September 21, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031
• Last Updated: September 21, 2026

Record last verified: 2026-08

Locations

CN (6)