Pirtobrutinib plus lisaftoclax and rituximab for relapsed or refractory DLBCL

A Prospective Study of Pirtobrutinib, Lisaftoclax, and Rituximab in the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)

This trial tests whether combining pirtobrutinib, lisaftoclax, and rituximab helps people with relapsed or refractory diffuse large B‑cell lymphoma who have had at least one prior systemic therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: pirtobrutinib, Chemotherapy, immunotherapy, rituximab
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07255963 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, single‑arm interventional trial giving a combination of pirtobrutinib, lisaftoclax, and rituximab to adults with relapsed or refractory DLBCL and measurable disease on PET‑CT. Eligible participants must have had at least one prior systemic therapy and meet organ function and performance status criteria. The protocol requires regular clinical and imaging follow‑up to measure response and safety. The trial is led at The First Affiliated Hospital of Soochow University in Suzhou, Jiangsu.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed relapsed or refractory DLBCL, PET‑CT measurable disease, at least one prior systemic therapy, ECOG 0–3, and adequate organ and marrow function are ideal candidates.

Not a fit: Patients with poor organ function, very short expected survival, uncontrolled infections, or contraindications to any study drug are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the combination could improve response rates or duration of response for patients with relapsed or refractory DLBCL.

How similar studies have performed: Components of this regimen (BTK inhibitors and BCL‑2 inhibitors with anti‑CD20 antibodies) have shown activity in other B‑cell lymphomas, but this specific triple combination in R/R DLBCL is novel and early‑phase.

Eligibility criteria

Inclusion Criteria:

1. ≥18 years old.
2. Capable of understanding and voluntarily signing written informed consent.
3. ECOG performance 0 \~ 3.
4. Anticipated survival ≥3 months
5. Histologically or cytologically confirmed DLBCL.
6. PET-CT-defined measurable disease with a short axis diameter of ≥1.5 cm.
7. Have received at least one prior line of systemic therapy for DLBCL.
8. Resolution of any prior treatment-related non-hematologic toxicities to Grade ≤1 or baseline.
9. Adequate Bone Marrow and Organ Function, defined as:

   Bone Marrow Function: ANC≥1.5 × 10⁹/L, Platelets ≥80 × 10⁹/L, Hemoglobin ≥80 g/L Hepatic Function: Total bilirubin ≤1.5 × ULN (≤3.0 × ULN if liver metastases present); AST/SGOT and ALT/SGPT ≤2.5 × ULN (≤5.0 × ULN if liver metastases present) Coagulation: INR and aPTT≤1.5 × ULN Renal Function: Serum creatinine ≤1.5 × ULN or estimated creatinine clearance (CrCl) ≥60 mL/min;
10. Subjects with childbearing or childbearing potential must be willing to practice birth control from the date of registration in this study to the follow-up period of the study.
11. Able to swallow tablets/capsules without difficulty.
12. Adhere to scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Prior treatment failure or resistance to pirtobrutinib or BCL2 inhibitors.
2. Prior Anticancer Therapy:Chemotherapy, radiotherapy, immunotherapy, or antibody-based anticancer therapy within the specified washout period.Traditional Chinese herbal medicine with antitumor indications.Small-molecule targeted therapy within 2 weeks before study treatment initiation. ADCs or cytotoxic therapy within 10 weeks before study treatment initiation.
3. Participation in another investigational drug study within 4 weeks prior to the first dose of study treatment.
4. Systemic corticosteroid therapy (\>5 days within 14 days prior to treatment) at doses exceeding \>10 mg/day dexamethasone (or equivalent) for CNS disease control.
5. Requiring ongoing anticancer therapy.
6. Uncontrolled or Severe Cardiovascular Disease,
7. Active infection requiring IV antibiotics or systemic antimicrobial therapy.
8. Active HBV/HCV:Exceptions. Inactive HBsAg carriers, HBV patients with sustained viral suppression (HBV-DNA \< LLOD),HCV-cured patients are allowed.
9. Clinically significant abnormalities affecting drug absorption or prior total gastrectomy/gastric banding.
10. History of hemorrhagic diathesis or requirement for long-term oral anticoagulation.
11. Prior allogeneic hematopoietic stem cell transplantation (HSCT) or planned allogeneic HSCT.
12. Women who are pregnant or breastfeeding.
13. Known allergy to the study drug or its excipients.
14. Active psychiatric illness or history of alcohol/drug abuse .
15. Any uncontrolled illness, organ dysfunction, or medical condition that, in the investigator's judgment, jeopardizes patient safety or adherence to study procedures.
16. Other conditions deemed inappropriate for study participation by the investigator.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Changju Qu

Conditions DLBCL - Diffuse Large B Cell Lymphoma; pirtobrutinib; Lisaftoclax; DLBCL