Philadelphia Chromosome Negative ALL, Acute Lymphoblastic Leukemia, Adult
Conditions
Keywords
Philadelphia Chromosome Negative Precursor B-Cell Acute Lymphoblastic Leukaemia, CAR-T cell, Venetoclax, Newly Diagnosed
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.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_PRODUCTCAR-T cells
CAR-T cells as consolidation therapy
DRUGVenetoclax
VEN
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | Up to 2 years post-registration | From CR1 to relapse, death from any cause or last follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRD-negative complete remission rate measured by flow cytometry. | After induction (4 week)] | No blasts were detected by flow cytometry when CR criteria were met after induction therapy. |
| Overall survival (OS) | Up to 5 years post-registration | From the date of registration to the date of death resulting from any cause. |
| 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 |
| 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 |
| 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. |
| The rate of adverse events | Up to 5 years post-registration | adverse events during the treatment |
Countries
China
Contacts
CONTACTJianxiang Wang, Dr
PRINCIPAL_INVESTIGATORJianxiang Wang, Dr
Institute of Hematology & Blood Diseases Hospital, China
Outcome results
None listed