Efficacy and Safety of Chemotherapy Combined With CAR-T Cells in Newly Diagnosed Adult Patients With Ph- B-ALL

Not Applicable

Recruiting

• Conditions: Philadelphia Chromosome Negative ALL; Acute Lymphoblastic Leukemia, Adult
• Interventions: Combination Product: CAR-T cells; Drug: Venetoclax

• Registration Number: NCT06481241
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Study Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-24
• Study Start: 2024-06-10
• Study First Submitted QC: 2024-06-28
• Study First Posted: 2024-07-01
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-06
• Primary Completion: 2026-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 77

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
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 pediatric-inspired regimen and venetoclax.
Chemotherapy and Sequential CAR-T Cells	Venetoclax	Ph-ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with pediatric-inspired regimen and venetoclax.

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
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.
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
Overall survival (OS)	Up to 5 years post-registration	From the date of registration to the date of death resulting from any cause.
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.
The rate of adverse events	Up to 5 years post-registration	adverse events during the treatment
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

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China