Efficacy and Safety of TKI Combined With Chemotherapy and Sequential CAR-T Cells in ND Adult Patients With Ph+ ALL
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
Institute of Hematology & Blood Diseases Hospital, China
82 participants
Jun 4, 2024
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- 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
Exclusion Criteria13
- 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
Interventions
CAR-T cells as consolidation therapy
BCL2 inhibitor
TKI
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06481228