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

Efficacy and Safety of Molecular Targeted Therapy Combined With Chemotherapy and Sequential CAR-T Cells in Newly Diagnosed Adult Patients With Philadelphia Chromosome-Positive B-cell Acute Lymphoblastic Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Philadelphia Positive Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, Adult
• Intervention / Treatment: Combination product: CAR-T cells; Drug: Venetoclax; Drug: Olverembatinib

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 Type: Interventional
• Enrollment (Estimated): 82
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianxiang Wang, Dr; Phone Number: 86-22-23608451; Email: wangjx@ihcams.ac.cn

Study Locations

• China
  • Tianjin, China, 300020
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital
    • Contact: Jianxiang Wang, Dr.; Phone Number: 86-22-23909120; Email: wangjx@medmail.com.cn
    • Principal Investigator: Jianxiang Wang, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged 18 years or older
2. Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia
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. Lymphoid blast crisis of chronic myelocytic leukemia (CML)
2. Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
3. 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.)
4. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
5. Known HIV seropositivity
6. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
7. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
8. 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
9. Female patients who are pregnant or breast feeding
10. Clinical manifestations of active CNS or extramedullary involvement with ALL
11. Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
12. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment
13. Other conditions assessed by the investigators to be inappropriate for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TKI Combined With Chemotherapy and Sequential CAR-T Cells; 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; CAR-T cells as consolidation therapy; Drug: Venetoclax; BCL2 inhibitor; Drug: Olverembatinib; TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival (DFS)	From CR1 to relapse, death from any cause or last follow-up	Up to 2 years post-registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	From the date of registration to the date of death resulting from any cause.	Up to 5 years post-registration
Event-free survival (EFS)	From the date of registration to the date of induction failure, relapse, death from any cause, or last follow-up	Up to 5 years post-registration
Cumulative rate of complete molecular response	The cumulative rate of patients achieving complete molecular remission	Up to 1 year post-registration
MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements	No clonal IG/TR rearrangements were detected by NGS	Up to 1 year post-registration
Cumulative incidence of relapse (CIR)	Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk.	Up to 2 years post-registration
The rate of adverse	adverse events during the treatment	Up to 5 years post-registration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interim analysis index	It is planned to conduct one interim analysis in the study: when the median follow-up date of patients reaches 1 year, the Independent Data Monitoring Committee (IDMC) will perform a hypothesis test by comparing the 1-year disease-free survival (DFS) rate (the primary endpoint) of the trial group with the 70% 1-year DFS rate of the historical control. The alpha (α) spending function will be calculated using the O'Brien-Fleming method. If the DFS rate of the trial group is found to be significantly superior to that of the historical control in the interim analysis and achieves statistical significance at the nominal significance level αk, the trial may be terminated early. If no statistically significant difference is observed between the two groups in the interim analysis, the investigators will decide whether to continue the trial based on practical circumstances.	From enrollment to 12 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Jianxiang Wang, Dr, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Venetoclax; Newly Diagnosed; CAR-T cell; Ph-Positive Acute Lymphoblastic Leukemia; olverembatinib
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; venetoclax; Immunotherapy, Adoptive; olverembatinib
• Other Study ID Numbers: IIT2024019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No