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

ConditionRichter Syndrome
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitute of Hematology & Blood Diseases Hospital, China

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • 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

    Drug

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

  • Pirtobrutinib

    Drug

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

  • Liposomal mitoxantrone

    Drug

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

Treatment groups

23 Participants
are divided into 1 treatment group
Group A: Rituximab, Pirtobrutinib, Lisaftoclax and Liposomal MitoxantroneExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

CR rate

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

Secondary outcomes

1

ORR

Time frame
At the end of 4-cycle(each cycle is 21 days) induction treatment period
2

DOR

Time frame
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.
3

PFS

Time frame
Up to 5 years
4

OS

Time frame
Up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Hematology & Blood Diseases Hospital, China

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: