Clinical trial NCT06481241: Efficacy and Safety of Chemotherapy Combined With CAR-T Cells in Newly Diagnosed Adult Patients With Ph- B-ALL
Official title: Efficacy and Safety of Chemotherapy Combined With CAR-T Cells in Newly Diagnosed Adult Patients With Philadelphia Chromosome-Negative B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Philadelphia Chromosome Negative ALL
Acute Lymphoblastic Leukemia, Adult
Keywords: Philadelphia Chromosome Negative Precursor B-Cell Acute Lymphoblastic Leukaemia
CAR-T cell
Venetoclax
Newly Diagnosed
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-07-01
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 relapsed/refractory (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- B-ALL patients achieving complete remission (CR) with 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.

Eligibility criteria: Inclusion Criteria:

1. De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification
2. Male or female patients aged 18 years or older
3. CD19 expression on blasts
4. Expected survival time greater than 3 months
5. 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%
6. Subject has provided written informed consent prior to any screening procedure

Exclusion Criteria:

1. Burkitt lymphoma/leukemia
2. Acute Leukemia of Ambiguous Lineage
3. Clinical manifestations of active CNS or extramedullary involvement with ALL
4. Female patients who are pregnant or breast feeding
5. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
6. Known HIV seropositivity
7. Clinically significant ventricular arrhythmias, unexplained syncope (not vasovagal) or sinus block, history of chronic bradycardia with a high degree of atrioventricular (AV) conduction block (unless a permanent pacemaker is implanted)
8. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
9. Other conditions assessed by the investigators to be inappropriate for this study

Primary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: Up to 2 years post-registration
Secondary outcomes:
measure: MRD-negative complete remission rate measured by flow cytometry.
timeFrame: After induction (4 week)]
measure: Overall survival (OS)
timeFrame: Up to 5 years post-registration
measure: Event-free survival (EFS)
timeFrame: Up to 5 years post-registration
measure: MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements
timeFrame: Up to 1 year post-registration
measure: Cumulative incidence of relapse (CIR)
timeFrame: Up to 2 years post-registration]
measure: The rate of adverse events
timeFrame: Up to 5 years post-registration
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Jianxiang Wang, Dr
role: PRINCIPAL_INVESTIGATOR
References: