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

Overview

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.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.

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.

Interventions

• Combination product CAR-T cells
  CAR-T cells as consolidation therapy
• Drug Venetoclax
  VEN

Primary outcome measures

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

Secondary outcome measures (6)

• MRD-negative complete remission rate measured by flow cytometry. [Time frame: After induction (4 week)]]
• Overall survival (OS) [Time frame: Up to 5 years post-registration]
• Event-free survival (EFS) [Time frame: Up to 5 years post-registration]
• MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements [Time frame: Up to 1 year post-registration]
• Cumulative incidence of relapse (CIR) [Time frame: Up to 2 years post-registration]]
• The rate of adverse events [Time frame: Up to 5 years post-registration]

Eligibility criteria

Inclusion criteria

• 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
• Male or female patients aged 18 years or older
• 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 criteria

• Burkitt lymphoma/leukemia
• Acute Leukemia of Ambiguous Lineage
• Clinical manifestations of active CNS or extramedullary involvement with ALL
• Female patients who are pregnant or breast feeding
• Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
• Known HIV seropositivity
• 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)
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Institute of Hematology & Blood Diseases Hospital — Tianjin

Identifiers

NCT: NCT06481241 · IIT2024020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗