Selinexor Combined With R-GDP Regimen for TP53-altered R/R DLBCL

Официальное название

Selinexor Combined With R-GDP Regimen for TP53-altered Relapsed/Refractory Diffuse Large B-cell Lymphoma: a Single Arm, Single Center, Phase II Study

Обзор

To evaluate the efficacy and safety of selinexor combined with R-GDP regimen in the treatment of patients with TP53-altered relapsed or refractory B-cell lymphoma.

Подробное описание

This study is a single-arm, open-label exploratory clinical trial. To evaluate the efficacy and safety of selinexor combined with R-GDP regimen in the treatment of patients with TP53-altered relapsed or refractory B-cell lymphoma.

Вмешательства

• Препарат SR-GDP
  Selinexor 40mg/d，po d1,8,15; rituximab 375mg/m2, iv d1; gemcitabine 1g/m2, iv d1,8; cisplatin 25mg/m2, iv d1-3; dexamethasone 40mg，po/iv d1-4 (If patient\>70y, the dosage should be changed to 20mg). Each cycle lasts for 21 days, with a maximum of 6 cycles of combination therapy. For patients who achieved PR or better response at the end of combination therapy, they will start receiving single-agent selinexor 40mg treatment (qw) in cycles of 28 days until disease progression (PD) or unacceptable

Первичные конечные точки

• Objective Response Rate [Срок оценки: At the end of Cycle 6 (each cycle is 21 days)]

Вторичные конечные точки (3)

• progression free survival [Срок оценки: Baseline up to data cut-off (up to approximately 2 years)]
• overall survival [Срок оценки: Baseline up to data cut-off (up to approximately 2 years)]
• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [Срок оценки: Up to 30 days after completion of study treatment]

Критерии участия

Критерии включения

• Age≥18
• Pathologically confirmed primary DLBCL or previously diagnosed indolent lymphoma (e.g., follicular lymphoma) transformation to DLBCL with TP53 deletion or mutation confirmed by FISH or next-generation sequencing.
• Received at least 1 but no more than 3 previous lines of systemic therapy for DLBCL, and was relapsed or refractory to the last line of therapy Salvage chemoimmunotherapy and subsequent stem cell transplantation are considered the same first-line systemic therapy Maintenance therapy will not be counted separately as first-line systemic therapy Radiotherapy for curative treatment of localized DLBCL lesions does not count as first-line systemic therapy
• Presence of measurable positron-emission tomography (PET) -positive lesions with at least one lymph node lesion long diameter (LDi) > 1.5 cm or an extra-nodal lesion LDi > 1 cm (according to the Lugano classification, 2014 version)
• Bone marrow function was good at screening Absolute neutrophil count (ANC) ≥1×109/L Platelet count ≥50×109/L (no platelet transfusion < 14 days before cycle 1 day 1, C1D1) Hemoglobin ≥8.0 g/dL (no red blood cell transfusion < 14 days before C1D1)
• Good liver and kidney function, namely:

AST or ALT ≤2.5× upper normal value limit (ULN), or ≤5×ULN in the presence of known lymphoma involving the liver Serum total bilirubin ≤2×ULN, or when Gilbert's syndrome or known lymphoma involves the liver≤5×ULN CrCl≥30 mL/min according to the Cockcroft-Gault formula

• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Estimated life expectancy at screening was > 3 months
• Agree to use a highly effective contraceptive during the study, which lasts for 12 months after the last dose of study treatment

Критерии исключения

• Patients who met any of the following exclusion criteria were not eligible for the study:

• Prior treatment with selinexor or another XPO1 inhibitor
• There are contraindications to any drug in the combination therapy
• Receipt of any standard or investigational anti-DLBCL therapy <21 days before C1D1 (including non-palliative radiotherapy, chemotherapy, immunotherapy, radioimmunotherapy, or any other anticancer therapy) (Palliative radiotherapy for non-target lesions was allowed)
• Undergone major surgery <14 days before C1D1
• Hematopoietic stem cell transplantation /CAR-T therapy requirements are as follows:

Autologous hematopoietic stem cell transplantation (HSCT) <100 days or allogeneic HSCT <180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic HSCT (or inability to discontinue GVHD therapy or preventive therapy) CAR-T cell infusion <90 days before cycle 1

• Presence of grade ≥2 neuropathy (CTCAE, v.5.0)
• Presence of any life-threatening disease, medical condition, or organ system dysfunction that is considered by the investigator to be likely affecting patient safety or adherence to study procedures
• Uncontrolled (i.e., clinically unstable) infection within 7 days before the first dose of study treatment and required treatment with intravenous antibiotics, antiviral drugs or antifungal drugs; However, prophylactic use of these agents was allowed.
• Patients with active HBV, HCV, or HIV infection. Participants who were HBsAg positive and/or HBcAb positive but HBV-DNA negative, and/or HCV antibody positive but HCV-RNA negative were allowed to participate (the upper limit of normal values for HBV-DNA and HCV-RNA were based on the values available at each participating center).
• Inability to swallow tablets, presence of a malabsorption syndrome, or any other condition that may interfere with absorption of the study drug
• Lactating or pregnant women
• Unable or unwilling to sign the ICF
• Patients who were considered by the investigator to be significantly below tolerable weight
• Patients who received live attenuated vaccine within 28 days prior to the first dose of study treatment

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 — Шанхай

Идентификаторы

NCT: NCT06062641 · RJ-XLYM-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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