Clinical Study of XNW5004 Combined With CHOP/CHOEP in the Treatment of Untreated Peripheral T-Cell Lymphoma

Официальное название

A Phase Ib/II Clinical Study of XNW5004 Combined With CHOP/CHOEP in the Treatment of Untreated Peripheral T-Cell Lymphoma

Обзор

In this study, the XNW5004 tablets combined with CHOP/CHOEP will be used for the treatment of newly diagnosed PTCL patients.

Вмешательства

• Препарат XNW5004 combined with CHOP (incremental)
  The XNW5004 protocol has preset four dosage groups: 400mg, 800mg, 1200mg and 1600mg, administered twice daily (BID). The CHOP regimen is administered at a fixed dose, for a total of 6 cycles. After completing the combined treatment and without disease progression, the subjects will continue to receive XNW5004 at 1200mg BID for maintenance therapy.
• Препарат XNW5004 combined with CHOEP (incremental)
  It is expected to conduct dose escalation studies for XNW5004 in combination with CHOEP using 1-3 dose groups. The CHOEP regimen will be administered at a fixed dose for a total of 6 cycles. After completing the combined treatment and without disease progression, the subjects will continue to receive XNW5004 at 1200mg BID for maintenance therapy.
• Препарат XNW5004 combined with CHOP (extended)
  Those who received the combination treatment of XNW5004 and CHOP, and who did not experience disease progression after the combined treatment, will continue to receive maintenance treatment with XNW5004 at a dose of 1200mg twice daily.
• Препарат XNW5004 combined with CHOEP (extended)
  Those who received the combination treatment of XNW5004 and CHOEP, and who did not experience disease progression after the combined treatment, will continue to receive maintenance treatment with XNW5004 at a dose of 1200mg twice daily.

Первичные конечные точки

• Ib/II:Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]. [Срок оценки: through study completion, an average of 1 year]
• II：Objective response rate (ORR) [Срок оценки: 36 months]
• Ib:Maximum tolerated dose (MTD) and/or the recommended Part 2 dose [Срок оценки: The first 21-day cycle of therapy]

Вторичные конечные точки (12)

• Ib/II:The maximum (peak) blood drug concentration (Cmax) is XNW5004 [Срок оценки: through study completion, an average of 1 year]
• Ib/II：XNW5004 Peak Time (Tmax) [Срок оценки: through study completion, an average of 1 year]
• Ib/II：The area under the blood drug concentration-time curve of XNW5004 (AUC) [Срок оценки: through study completion, an average of 1 year]
• Ib/II:The maximum (peak) blood drug concentration in the steady state (Css,max) [Срок оценки: through study completion, an average of 1 year]
• Ib/II:XNW5004 Steady-state Baseline Concentration (Css, min) [Срок оценки: through study completion, an average of 1 year]
• Ib/II:The area under the blood drug concentration-time curve (AUCss) under steady-state conditions of XNW5004 [Срок оценки: through study completion, an average of 1 year]
• Ib/II:XNW5004 Elimination Half-Life (T1/2) [Срок оценки: through study completion, an average of 1 year]
• Ib/II:Pharmacodynamic indicators, the relative change of H3K27me3 (trimethylation of lysine at position 27 of histone H3) compared to the baseline of histone H3 [Срок оценки: through study completion, an average of 1 year]
• Ib/II:Objective Response Rate (ORR) [Срок оценки: 36 months]
• Ib/II:Disease Control Rate (DCR) [Срок оценки: 36 months]
• Ib/II:Duration of response (DOR) [Срок оценки: 36 months]
• Ib/II:Progression free survival (PFS) [Срок оценки: 36 months]

Критерии участия

Критерии включения

• Age 18 to 75 years (inclusive); both genders are eligible.
• Pathologically confirmed peripheral T-cell lymphoma (PTCL).
• No prior systemic anti-PTCL therapy.
• At least one measurable lesion as the basis for evaluation: nodal lesions with a long diameter > 1.5 cm; extranodal lesions with a long diameter > 1.0 cm.
• Life expectancy of at least 12 weeks.
• ECOG performance status score of 0-1.
• Vital organ function reserves meet the following requirements:
• Hematopoietic function:
• White blood cell count >= 3.5 x 10\^9/L (no G-CSF administration within 1 week before the screening blood test, and no long-acting leukocyte-elevating agent administration within 2 weeks)
• Platelet count >= 75 x 10\^9/L (no platelet transfusion or TPO receptor agonist administration within 1 week before the screening blood test)
• Hemoglobin >= 80 g/L (no red blood cell transfusion or EPO administration within 1 week before the screening blood test)
• Hepatic function: serum total bilirubin <= 1.5 x ULN (<= 3 x ULN for Gilbert's syndrome), and ALT and AST <= 2.5 x ULN; for subjects with liver infiltration, ALT/AST <= 5 x ULN; for subjects with liver and/or bone infiltration, alkaline phosphatase <= 5 x ULN
• Renal function: serum creatinine <= 1.5 x ULN or estimated creatinine clearance >= 60 mL/min according to the Cockcroft-Gault formula
• Left ventricular ejection fraction (LVEF) >= 50%
• International normalized ratio (INR) <= 1.5 x ULN, or prothrombin time (PT) and activated partial thromboplastin time (APTT) <= 1.5 x ULN
• Women of childbearing potential must have a negative serum pregnancy test before entering this study and agree to use effective contraception from the start of the study until at least 6 months after the last dose of the investigational drug. Female subjects who are not capable of childbearing must have been naturally amenorrheic for at least 12 months and be confirmed by a specialist physician as having no reproductive function based on female hormone testing; or have undergone bilateral oophorectomy, hysterectomy, or tubal ligation at least 6 weeks prior to screening. Male subjects must agree to use adequate contraceptive measures from the start of the study until at least 6 months after the last dose of the investigational drug, and must not donate sperm.
• Provide a signed and dated written informed consent form prior to undergoing study-specific procedures, and be able to comply with clinical visits and study-related procedures.

Критерии исключения

• Prior treatment with any anti-tumor therapy, including but not limited to: chemotherapy, immunotherapy, radiotherapy, targeted therapy, anti-tumor traditional Chinese medicine, or anti-tumor investigational drugs.
• Subjects with known hypersensitivity to the investigational drug or its active ingredients or excipients.
• Subjects who have undergone major surgery within 4 weeks prior to the first dose of the investigational drug, or who plan to undergo major surgery during the study period (except for procedures such as puncture or lymph node biopsy).
• Prior or planned allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
• Receipt of steroid hormones for anti-tumor purposes (daily dose > 20 mg prednisone or equivalent dose of other glucocorticoids) within 7 days prior to the first dose of the investigational drug; or diseases requiring systemic treatment with steroid hormones (daily dose > 10 mg prednisone or equivalent dose of other glucocorticoids) or other immunosuppressive drugs within 14 days prior to the first dose of the investigational drug. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal replacement therapy with a daily dose <= 10 mg prednisone or equivalent dose of other glucocorticoids are permitted.
• Subjects who have taken known moderate or strong CYP3A4 inhibitors/inducers within 14 days prior to the first dose.
• Receipt of live virus vaccine (including attenuated live vaccine) within 28 days prior to dosing. Inactivated vaccines are permitted.
• History of psychotropic substance abuse or drug addiction.
• History of other malignancies within 3 years prior to enrollment that do not meet clinical cure criteria. The following are exceptions: basal cell carcinoma or squamous cell carcinoma of the skin that can be treated locally and has been cured, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
• Mycosis fungoides, Sezary syndrome, and primary cutaneous T-cell lymphoma.
• Presence of central nervous system involvement.
• Presence of testicular or breast involvement.
• Prior or current hemophagocytic syndrome.
• Prior or current immune thrombocytopenia, autoimmune hemolytic anemia, aplastic anemia, or other primary or secondary hematological diseases that may affect bone marrow function other than the primary malignancy.
• Prior or current acute myeloid leukemia (AML).
• Prior or current T-cell lymphoblastic lymphoma (T-LBL) or T-cell lymphoblastic leukemia (T-ALL).
• History of any myeloid malignancy, including myelodysplastic syndrome (MDS), or abnormal laboratory markers associated with MDS or myeloproliferative neoplasm (MPN).
• Prior or concomitant central nervous system disorders, including but not limited to: epilepsy, paralysis, stroke, severe brain injury, Alzheimer's disease, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, etc.
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Acute myocardial infarction within 12 months prior to the first dose
• Unstable angina pectoris
• Congestive heart failure (New York Heart Association functional class III or IV)
• Uncorrected serious arrhythmia, hypertension >= 150/100 mmHg
• Prolonged QTc interval (defined as > 450 ms for males and > 470 ms for females, by Fredericia's formula)
• Prior history of other major cardiovascular diseases (e.g., valve replacement, coronary artery bypass grafting, etc.)
• Tumor invasion of surrounding vital organs and blood vessels (e.g., heart and pericardium, trachea, esophagus, aorta, superior vena cava, etc.) with risk of bleeding, or risk of tracheoesophageal fistula or esophagopleural fistula.
• Subjects with clinically symptomatic pleural effusion, ascites, or pericardial effusion that is poorly controlled despite repeated treatment.
• Active severe systemic infection: a washout period of at least 2 weeks is required after completion of antifungal therapy (whether administered intravenously or orally); a washout period of at least 1 week is required after completion of other intravenous anti-infective therapy; other oral anti-infective therapies must be discontinued before the first dose of the investigational drug.
• Active tuberculosis under treatment.
• HIV-positive or syphilis (Anti-TP) positive subjects (subjects with negative syphilis non-specific antibody test results and judged by the investigator to have been cured of syphilis are not excluded).
• HBsAg positive with HBV-DNA copy number above the lower limit of normal detection, or HBcAb positive with HBV-DNA copy number above the lower limit of normal detection; HCV antibody positive with HCV-RNA copy number above the lower limit of normal detection.
• Subjects who are unable to swallow, or have active gastrointestinal inflammation, chronic diarrhea, known diverticular disease, or a history of gastrectomy or gastric banding that may affect drug absorption. However, gastroesophageal reflux treated with proton pump inhibitors is permitted (if there is no potential for drug interaction).
• Known hemorrhagic diathesis such as von Willebrand disease or hemophilia.
• Females who are pregnant or breastfeeding.
• Subjects who may not be able to complete the study for other reasons or whom the investigator considers should not be enrolled.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07730515 · XNW5004-Ib/II-05

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗