Efficacy and Safety of TKI Combined With Chemotherapy and Sequential CAR-T Cells in ND Adult Patients With Ph+ ALL

Официальное название

Efficacy and Safety of Molecular Targeted Therapy Combined With Chemotherapy and Sequential CAR-T Cells in Newly Diagnosed Adult Patients With Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia

Обзор

In recent years, immunotherapy (eg. blinatumomab, inotuzumab ozogamicin, CAR-T cells) has demonstrated a high safety and efficacy profile in relapsed/refractory (R/R）B-ALL. The available data suggest that the advancement of immunotherapy from R/R field to the frontline setting may be an important approach to increase the depth of remission, which ultimately translates into a survival benefit. In this study, the investigators propose a treatment regimen using CAR-T cell therapy as a consolidation method for Ph+ ALL patients achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy, aiming to reduce the total cycles of chemotherapy and related toxicities, shorten length of hospitalization, and ultimately improve patients' survival and quality of life.The study endpoints include 2-year disease-free survival (DFS) rate, overall survival (OS) rate, event-free survival (EFS) rate, cumulative molecular remission rate, immune repertoire-minimal residual disease (MRD) remission rate, cumulative relapse rate, treatment-related toxicities, and quality of life. Additionally, an interim analysis will be conducted, with the 1-year DFS rate as the key index for this analysis.

Подробное описание

The CAR-T cells were murine-derived second-generation CD19 CAR-T with a co-stimulation domain of 4-1BB, and the infusion dose was 1×10\^6/kg CAR+ cells in a single infusion.

Вмешательства

• Комбинированный продукт CAR-T cells
  CAR-T cells as consolidation therapy
• Препарат Venetoclax
  BCL2 inhibitor
• Препарат Olverembatinib
  TKI

Первичные конечные точки

• Disease-free Survival (DFS) [Срок оценки: Up to 2 years post-registration]

Вторичные конечные точки (6)

• Overall survival (OS) [Срок оценки: Up to 5 years post-registration]
• Event-free survival (EFS) [Срок оценки: Up to 5 years post-registration]
• Cumulative rate of complete molecular response [Срок оценки: Up to 1 year post-registration]
• MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements [Срок оценки: Up to 1 year post-registration]
• Cumulative incidence of relapse (CIR) [Срок оценки: Up to 2 years post-registration]
• The rate of adverse [Срок оценки: Up to 5 years post-registration]

Критерии участия

Критерии включения

• Male or female patients aged 18 years or older
• Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia
• CD19 expression on blasts
• Expected survival time greater than 3 months
• Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%
• Subject has provided written informed consent prior to any screening procedure

Критерии исключения

• Lymphoid blast crisis of chronic myelocytic leukemia (CML)
• Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
• Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
• Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
• Known HIV seropositivity
• History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
• Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
• Another malignancy diagnosed and treated within 5 years prior to diagnosis or previously diagnosed with another malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ that has been completely excised should not be excluded
• Female patients who are pregnant or breast feeding
• Clinical manifestations of active CNS or extramedullary involvement with ALL
• Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
• Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
• Other conditions assessed by the investigators to be inappropriate for this study

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

• Institute of Hematology & Blood Diseases Hospital — Тяньцзинь

Идентификаторы

NCT: NCT06481228 · IIT2024019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗