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

NCT06481241 | Recruiting

• 1 other identifier: IIT2024020
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia, Adult; Philadelphia Chromosome Negative ALL

Keywords

Philadelphia Chromosome Negative Precursor B-Cell Acute Lymphoblastic Leukaemia; CAR-T cell; Venetoclax; Newly Diagnosed

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  From CR1 to relapse, death from any cause or last follow-up

  Up to 2 years post-registration

Secondary Outcomes (6)

• MRD-negative complete remission rate measured by flow cytometry.

  After induction (4 week)]

• Overall survival (OS)

  Up to 5 years post-registration

• Event-free survival (EFS)

  Up to 5 years post-registration

• MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements

  Up to 1 year post-registration

• Cumulative incidence of relapse (CIR)

  Up to 2 years post-registration]

Other Outcomes (1)

• Interim analysis index

  From enrollment to 12 months

Study Arms (1)

Chemotherapy and Sequential CAR-T Cells

EXPERIMENTAL

Ph-ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with pediatric-inspired regimen and venetoclax.

Combination Product: CAR-T cells; Drug: Venetoclax

Interventions

Venetoclax DRUG

VEN

Also known as: Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Chemotherapy and Sequential CAR-T Cells

CAR-T cells COMBINATION_PRODUCT

CAR-T cells as consolidation therapy

Chemotherapy and Sequential CAR-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy, Adoptive; venetoclax; Genes, bcl-2

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Proto-Oncogenes; Oncogenes; Genes, Neoplasm; Genes; Genome Components; Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Jianxiang Wang, Dr

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxiang Wang, Dr

CONTACT

86-22-23608451; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: July 1, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

CN (1)