An Open-label, Single-arm, Multicenter Phase II Clinical Study of Azacitidine, Chidamide Combined With PD-1 Monoclonal Antibody in the Treatment of Refractory/Relapsed Peripheral T-cell Lymphoma.

Обзор

An Open-Label, Single-Arm, Multicenter Phase II Clinical Study to Evaluate the Efficacy of Azacitidine, Chidamide, and PD-1 Monoclonal Antibody in the Treatment of Refractory/Relapsed Peripheral T-Cell Lymphoma.

Вмешательства

• Препарат Azacitidine (AZA)
  Azacitidine 100 mg is administered subcutaneously once daily from day 1 to day 7. The PD-1 monoclonal antibody 200 mg is administered by intravenous infusion on day 1. Chidamide 20 mg is administered orally twice weekly.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: From first dose of study drug until disease progression, initiation of new anti-cancer therapy, or study completion (up to 24 months).]
• Complete Response Rate (CRR) [Срок оценки: From first dose of study drug until disease progression, initiation of new anti-cancer therapy, or study completion (up to 24 months).]

Вторичные конечные точки (1)

• Progression-free survival（PFS） [Срок оценки: Assessed every 12 weeks during the treatment and follow-up period until disease progression or study completion (up to 2 years).]

Критерии участия

Критерии включения

• Age ≥18 years and ≤75 years, male or female.
• Histologically confirmed peripheral T-cell lymphoma (PTCL) by the investigating center, including: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALK-negative or ALK-positive); angioimmunoblastic T-cell lymphoma; enteropathy-associated T-cell lymphoma; NK/T-cell lymphoma; and other PTCL subtypes deemed eligible by the investigator.
• Relapsed or refractory disease after at least one prior line of systemic therapy. Relapse is defined as disease recurrence after complete response (CR) or progression after partial response (PR) or stable disease (SD). Refractory disease is defined as progressive disease (PD) after 2 cycles of therapy, or SD after 4 cycles of therapy, or failure to achieve response after adequate last-line therapy (e.g., at least 2-3 cycles of systemic chemotherapy without remission), or progression during treatment.
• Patients considered ineligible for autologous hematopoietic stem cell transplantation by the investigator, or those who refuse such treatment.
• At least one measurable or evaluable lesion according to the Lugano 2014 classification. Measurable lesion: nodal lesion with longest diameter >1.5 cm and shortest diameter >1.0 cm on CT/PET-CT or MRI; or extranodal lesion with longest diameter >1.0 cm. Evaluable lesion: nodal or extranodal focal uptake on 18F-FDG/PET higher than liver with PET and/or CT features consistent with lymphoma.
• ECOG performance status 0-2.
• Life expectancy ≥3 months.
• Adequate organ and bone marrow function defined as:

• Hematology: WBC ≥2.0×10⁹/L (≥1.0×10⁹/L if with bone marrow involvement), ANC ≥1.0×10⁹/L (≥0.5×10⁹/L if with bone marrow involvement), PLT ≥50×10⁹/L (≥30×10⁹/L if with bone marrow involvement), HGB ≥7.0 g/dL; no granulocyte growth factor support, platelet or RBC transfusion within 7 days prior to testing.
• Liver function: TBIL ≤1.5×ULN (≤3.0×ULN with liver involvement); ALT and AST ≤2.5×ULN (≤5.0×ULN with liver involvement).
• Renal function: Serum Cr ≤1.5×ULN.
• Coagulation: INR ≤1.5×ULN; PT and APTT ≤1.5×ULN (unless on anticoagulant therapy with PT/APTT within therapeutic range at screening).
• Thyroid function: TSH, FT4, and FT3 within ±10% of normal range (Note: TSH abnormalities due to non-autoimmune causes are acceptable).
• Cardiac function: Left ventricular ejection fraction ≥50%, no organic arrhythmia, no significant abnormalities in cardiac enzymes.

Критерии исключения

• History of other malignancies within the past 5 years, except for those treated with curative intent (e.g., basal cell carcinoma of the skin, carcinoma in situ).
• Patients with significant dysfunction of major organs.
• Known involvement of central nervous system (CNS) lymphoma.
• History of active bleeding or newly diagnosed thrombotic disease, or those with bleeding tendency receiving anticoagulant therapy.
• Known history of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS).
• Patients with active chronic hepatitis B or active hepatitis C.
• Systemic corticosteroid therapy or other immunosuppressive therapy required for any condition within 14 days prior to initiation of study treatment.
• Active autoimmune disease requiring systemic treatment within the past two years. Patients with autoimmune diseases not requiring systemic treatment in the past two years may be enrolled.
• Major surgery within 28 days prior to enrollment, or less than 6 weeks after major organ surgery.
• Administration of live attenuated vaccines within 4 weeks prior to enrollment or planned during the study period (influenza vaccines excluded).
• Pregnant or lactating women, and subjects of childbearing potential unwilling to use effective contraception.
• Psychiatric disorders or individuals unable to provide informed consent.
• Active infection, except for tumor-related B-symptom fever.
• Poorly controlled cardiac symptoms or diseases, including:

i. NYHA Class III or higher heart failure ii. Unstable angina iii. Myocardial infarction within the past year iv. Clinically significant arrhythmias

• Any other condition deemed by the investigator to make the subject unsuitable for study participation.

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

• The Second Affiliated Hospital of Soochow University Suzhou — Сучжоу

Публикации

• Angelos MG, Ballard HJ, Barta SK. Advances and Personalized Approaches in the Frontline Treatment of T-Cell Lymphomas. J Pers Med. 2022 Feb 11;12(2):267. doi: 10.3390/jpm12020267. PMID 35207754
• Foley NC, Mehta-Shah N. Management of Peripheral T-cell Lymphomas and the Role of Transplant. Curr Oncol Rep. 2022 Nov;24(11):1489-1499. doi: 10.1007/s11912-022-01310-3. Epub 2022 Aug 10. PMID 35947286

Идентификаторы

NCT: NCT07598578 · JD-LK2024096-I01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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