Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients (Smart Trial)

Официальное название

Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients: a Single-arm, Multicenter, Phase II Clinical Trial (Smart Trial)

Обзор

This is a prospective, single-arm, multi-center, phase II clinical trial to evaluate the efficacy and safety of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated TP53-mutated diffuse large B-cell lymphoma (DLBCL) patients.

Подробное описание

The purpose of this phase II clinical trial is to evaluate the efficacy and safety of selinexor in combination with R-CHOP for untreated TP53-mutated DLBCL patients.

The induction phase consisted of 8 cycles of selinexor in combination with R-CHOP. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.

The primary endpoint is complete response rate.

Вмешательства

• Препарат Selinexor Oral Tablet [Xpovio]
  Selinexor (60mg po D1, 8) is added from the second cycle of R-CHOP regimen.
• Препарат R-CHOP Protocol
  Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Первичные конечные точки

• Complete response rate (CRR) [Срок оценки: Up to 8 cycles (each cycle is 21 days)]

Вторичные конечные точки (7)

• Disease-free survival (DFS) [Срок оценки: From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
• Objective response rate (ORR) [Срок оценки: Up to 8 cycles (each cycle is 21 days)]
• Progression-free survival (PFS) [Срок оценки: From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
• Overall survival (OS) [Срок оценки: From the date of enrollment until the date of death from ant cause, assessed up to 24 months]
• Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0 [Срок оценки: Through study completion, an average of 2 years]
• Duration of response (DOR) [Срок оценки: From date of the first CR or PR to the first documented progressive disease or death, whichever occurred earlier, assessed up to 24 months]
• Time to response (TTR) [Срок оценки: From the date of enrollment until the first response, assessed up to 24 weeks]

Критерии участия

Критерии включения

• Subjects fully understand and voluntarily participate in this study and sign informed consent.
• Aged ≥18 and ≤80 years, no gender limitation.
• Histologically confirmed DLBCL with TP53 mutations (allowing transformed or concurrent indolent B-cell non-Hodgkin lymphoma)
• No prior systemic anti-lymphoma therapy; prior local radiotherapy alone is permitted.
• There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
• Expected survival ≥ 3 months.
• Adequate function of bone marrow, liver, and kidney.

Критерии исключения

• DLBCL with Hodgkin lymphoma, T-cell lymphoma, or other non-B-cell lymphoma; Richter transformation.
• DLBCL with central nervous system invasion.
• The patients had previously received XPO1 inhibitors.
• The patients have contraindications to any drug in the combined treatment.
• Patients with chronic active hepatitis B or active hepatitis C. If the background hepatitis B surface antigen (HBsAg) and/or hepatitis B core Antibody (HBcAb) or hepatitis C Virus (HCV) antibody are positive, the further determination for Hepatitis B Virus (HBV) DNA (no more than 2500 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the assay) can be included. The patients with HBsAg and/or HBcAb positive need to receive anti-HBV drugs.
• Patients with the infection of human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome.
• Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
• Pregnant and lactating women and subjects of childbearing age who do not want to use contraception.
• Mentally ill persons or persons unable to obtain informed consent.
• Any condition deemed unsuitable 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 · 2 центра

• Sun yat-sen university cancer center — Гуанчжоу
• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06517511 · B2024-333-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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