Efficacy and Safety of TKI Combined With Chemotherapy and Sequential CAR-T Cells in ND Adult Patients With Ph+ ALL

NCT06481228 | Recruiting

• 1 other identifier: IIT2024019
• Study Type: interventional
• Target: 82
• 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 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+ ALL patients achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity 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

Philadelphia Positive Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, Adult

Keywords

Ph-Positive Acute Lymphoblastic Leukemia; CAR-T cell; Venetoclax; olverembatinib; 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)

• Overall survival (OS)

  Up to 5 years post-registration

• Event-free survival (EFS)

  Up to 5 years post-registration

• Cumulative rate of complete molecular response

  Up to 1 year 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)

TKI Combined With Chemotherapy and Sequential CAR-T Cells

EXPERIMENTAL

Ph+ALL patients receiving CAR-T cells as consolidation therapy after achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy.

Combination Product: CAR-T cells; Drug: Venetoclax; Drug: Olverembatinib

Interventions

CAR-T cells COMBINATION_PRODUCT

CAR-T cells as consolidation therapy

TKI Combined With Chemotherapy and Sequential CAR-T Cells

Venetoclax DRUG

BCL2 inhibitor

TKI Combined With Chemotherapy and Sequential CAR-T Cells

Olverembatinib DRUG

TKI

TKI Combined With 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:

• Male or female patients aged 18 years or older
• Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia
• 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:

• Lymphoid blast crisis of chronic myelocytic leukemia (CML)
• Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
• Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
• Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
• Known HIV seropositivity
• History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
• Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL)
• Another malignancy diagnosed and treated within 5 years prior to diagnosis or previously diagnosed with another malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ that has been completely excised should not be excluded
• Female patients who are pregnant or breast feeding
• Clinical manifestations of active CNS or extramedullary involvement with ALL
• Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of \>7.5%. Patients with preexisting, well-controlled diabetes are not excluded
• 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; olverembatinib

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

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 4, 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)