Efficacy and Safety of TKI Combined With Chemotherapy and Sequential CAR-T Cells in ND Adult Patients With Ph+ ALL
- Conditions
- Philadelphia Positive Acute Lymphoblastic LeukemiaAcute Lymphoblastic Leukemia, Adult
- Interventions
- Registration Number
- NCT06481228
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 82
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TKI Combined With Chemotherapy and Sequential CAR-T Cells CAR-T cells Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy. TKI Combined With Chemotherapy and Sequential CAR-T Cells Venetoclax Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy. TKI Combined With Chemotherapy and Sequential CAR-T Cells Olverembatinib Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy.
- Primary Outcome Measures
Name Time Method Disease-free Survival (DFS) Up to 2 years post-registration From CR1 to relapse, death from any cause or last follow-up
- Secondary Outcome Measures
Name Time Method Event-free survival (EFS) Up to 5 years post-registration From the date of registration to the date of induction failure, relapse, death from any cause, or last follow-up
Cumulative rate of complete molecular response Up to 1 year post-registration The cumulative rate of patients achieving complete molecular remission
MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements Up to 1 year post-registration No clonal IG/TR rearrangements were detected by NGS
The rate of adverse Up to 5 years post-registration adverse events during the treatment
Overall survival (OS) Up to 5 years post-registration From the date of registration to the date of death resulting from any cause.
Cumulative incidence of relapse (CIR) Up to 2 years post-registration Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk.
Trial Locations
- Locations (1)
Institute of Hematology & Blood Diseases Hospital
🇨🇳Tianjin, China