Pirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Официальное название

A Study of Pirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin (Pirto-R-GemOx±Pola) in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Обзор

This is a prospective, single arm trial in patients with ≥ 18 years with relapsed and refractory DLBCL. Aim of this study is to evaluate the efficacy and safety of pirtobrutinib in combination with rituximab, gemcitabine, and oxaliplatin with or without polatuzumab vedotin (Pirto-R-GemOx±pola) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) previously treated with covalent BTK inhibitors.

Вмешательства

• Препарат Pirtobrutinib
  Dose:200mg，d1-21
• Препарат R-GemOx
  Dose: Rituximab: 375mg/m2, d1; Gemcitabine: 1000mg/m2, d2; Oxaliplatin:100mg/m2, d2
• Препарат Polatuzumab Vedotin
  Dose: 1.8mg/kg，iv，d1 (For patient who is CD79b positive and has not previously received polatuzumab Vedotin)

Первичные конечные точки

• complete response rate(CRR) [Срок оценки: Up to 6 cycles (each cycle is 21 days)]

Вторичные конечные точки (4)

• Objective response rate(ORR) [Срок оценки: Up to 6 cycles (each cycle is 21 days) ± pola]
• Progression-free survival (PFS) [Срок оценки: Up to 6 cycles (each cycle is 21 days)]
• Overall Survival (OS) [Срок оценки: up to 6 cycles(each cycle is 21 days)]
• undetectable MRD rate [Срок оценки: Up to 6 cycles (each cycle is 21 days) ± pola]

Критерии участия

Критерии включения

• Histologically confirmed DLBCL (2016 WHO criteria) of MCD, BN2, N1 subtypes, double-expressor, intravascular large B-cell lymphoma, or other BTK-sensitive subtypes
• Disease progression/relapse after covalent BTK inhibitor therapy
• ≥1 measurable lesion (nodal >15mm/extranodal >10mm) on PET/CT within 28 days
• Eastern Cooperative Oncology Group (ECOG) 0-2
• age ≥18 years
• Adequate organ function:

ANC ≥0.5×10⁹/L ；Platelets ≥50×10⁹/L (transfusion-independent)；Bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN；Cr ≤1.5×ULN or CrCl ≥30mL/min；LVEF ≥50% (NYHA class <III)

• Life expectancy >3 months
• Sign the written ICF, and be able to comply with the visits and related procedures stipulated in the protocol;
• Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last treatment.

Критерии исключения

• DLBCL with central nervous system (CNS) or meningeal involvement
• Histologically transformed DLBCL
• Contraindications or hypersensitivity to any drug in the combination regimen
• Major surgery within 4 weeks prior to treatment (excluding vascular access placement or biopsy)
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or compliance with study procedures
• Poorly controlled cardiac clinical symptoms or diseases, including:

i. NYHA Class II or higher heart failure ii. Unstable angina iii. Myocardial infarction within 1 year iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment/intervention

• Active hemorrhage
• Poorly controlled systemic bacterial, viral, fungal, or parasitic infections (excluding fungal nail infections), or other clinically significant active diseases that render patients unsuitable for trial participation per investigator assessment
• Patients with:Active chronic hepatitis B or C.Positive HBsAg and/or HBcAb or HCV antibodies at screening must demonstrate HBV DNA ≤2,500 copies/mL (or 500 IU/mL) to exclude active HBV/HCV infection requiring treatment.HBsAg/HBcAb-positive patients must receive antiviral prophylaxis.

HIV-infected patients and/or AIDS patients

• Inability to swallow tablets, malabsorption syndrome, or any gastrointestinal disorder/ dysfunction that may impair drug absorption
• Lactating or pregnant women
• Psychiatric disorders or inability to provide informed consent
• Any other condition deemed unsuitable for study participation by the investigator

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07122609 · pirto-R-Gemox

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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