BCL-2 Inhibitors Combined with the HyperCVAD Regimen for Newly Diagnosed T-lymphoblastic Leukemia/lymphoma.

The Efficacy and Safety of BCL-2 Inhibitors Combined with the HyperCVAD Regimen in the Treatment of Newly Diagnosed T-lymphoblastic Leukemia/ Lymphoma

The experimental group included patients diagnosed with T-ALL/LBL (T-lymphoblastic leukemia/ lymphoma) at initial diagnosis, who received treatment with BCL-2 inhibitors combined with the Hyper CVAD regimen. The control group consisted of patients diagnosed with T-ALL/LBL from multiple centers, for whom basic information, disease information, treatment details, and efficacy data were collected. Propensity score matching was conducted with historical data (matching factors included age, gender, initial LDH levels, and the presence or absence of a large mediastinal mass at diagnosis) to compare the advantages and disadvantages of the experimental regimen with previous induction treatment protocols. The primary endpoint was the complete remission (CR) rate after induction chemotherapy, while secondary endpoints included duration of remission (DOR), progression-free survival (PFS), overall survival (OS), and the occurrence of adverse events. This study aims to provide a more effective and safer treatment option for patients with T-LBL.

Study Overview

• Status: Recruiting
• Conditions: Lymphoblastic Leukemia, Acute T-cell; Lymphoblastic Lymphoma, Adult
• Intervention / Treatment: Drug: BCL-2 inhibitors combined with the HyperCVAD regimen; Other: Propensity score matching historical data

• Study Type: Interventional
• Enrollment (Estimated): 206
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xianmin Song，MD; Phone Number: +8613501672508; Email: shongxm@139.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria Age 18-60 years, regardless of gender; Expected survival time greater than 12 weeks; ECOG score 0-2; Pathologically or flow cytometrically confirmed as T-cell lymphoblastic lymphoma, with less than 25% tumor cell proportion in bone marrow smears;

Liver and kidney function, as well as cardiopulmonary function, meet the following requirements:

Creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 mL/min; Left ventricular ejection fraction greater than 50%, with no clinically significant ECG changes; Baseline oxygen saturation greater than 92% Total bilirubin ≤1.5×ULN; ALT and AST ≤3×ULN Able to understand the trial and has signed the informed consent form Exclusion Criteria A history of acute T-cell leukemia, T-cell lymphoma, or T-cell lymphoblastic lymphoma within the past 5 years, except for adequately treated carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery, or thyroid cancer after radical surgery Active bacterial, viral, or fungal infections that require treatment and are not controlled; those who are HBsAg or HBcAb positive, with peripheral blood HBV DNA ≥ the lower limit of detection; individuals who are positive for hepatitis C virus antibodies and have positive peripheral blood HCV RNA; individuals who test positive for syphilis (TRUST test); individuals who are positive for human immunodeficiency virus (HIV) antibodies Dysfunction of important organs (cardiovascular, pulmonary) or a history of active gastrointestinal bleeding within the past 3 months; individuals with uncontrolled hypertension, hypertensive crisis, or a history of hypertensive encephalopathy, and a history or evidence of significant cardiovascular risk, including any of the following: congestive heart failure, unstable angina, clinically significant arrhythmias (e.g., ventricular fibrillation, ventricular tachycardia); a history of arterial thrombosis within the past 3 months (e.g., stroke, transient ischemic attack); a history of symptomatic deep vein thrombosis, pulmonary embolism within the past 6 months, or a history of coronary angioplasty, defibrillation, or any clinical complications or diseases that may pose a risk to the participant's safety or interfere with the evaluation, procedures, or completion of the study Any uncontrolled active disease that may interfere with participation in the trial; Active, uncontrolled central nervous system diseases or a history of central nervous system disease requiring treatment (e.g., epilepsy) Pregnant or breastfeeding women; and individuals planning to become pregnant within 1 year after infusion, during treatment, or after treatment ends Presence of uncontrolled active infections (except for simple urinary tract infections or upper respiratory infections Known allergies to any components of cyclophosphamide, doxorubicin, vincristine, cytarabine, methotrexate, etc.

Any situation that the investigator believes would compromise participant safety or interfere with the study objectives, or any individual deemed inappropriate for participation by the investigator Individuals with diseases affecting their ability to sign the written informed consent form or comply with study procedures; those unwilling or unable to adhere to study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCL-2 inhibitors combined with the HyperCVAD regimen for newly diagnosed T-ALL/LBL	Drug: BCL-2 inhibitors combined with the HyperCVAD regimen; BCL-2 inhibitors combined with the HyperCVAD regimen for newly diagnosed adult T-ALL/LBL
Other: propensity score matching with historical data	Other: Propensity score matching historical data; Propensity score matching was conducted with historical data (matching factors included age, gender, initial LDH levels, and the presence or absence of a large mediastinal mass at diagnosis) to compare the advantages and disadvantages of the experimental regimen with previous induction treatment protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	adverse events during research	at the end of cycle 2(each cycle is 28 days)
The best overall response rate	complete remission and partial remission	at the end of cycle 2（each cycle is 28 days）
Evaluate the best complete remission rate (CR)		at the end of cycle 4 of chemotherapy（each cycle is 28 days）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of remission	Duration of remission	1 year
OS	1 year overall survival	1 year
OS	2 year overall survival	2 year
PFS	1 year progression free survival	1 year
PFS	2 year progression free survival	2 year
the proportion of successful bridging to allogeneic hematopoietic stem cell transplantation	he proportion of successful bridging to allogeneic hematopoietic stem cell transplantation	the end of the study

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2024
• Primary Completion (Estimated): August 7, 2026
• Study Completion (Estimated): August 7, 2027

Study Registration Dates

• First Submitted: September 3, 2024
• First Submitted That Met QC Criteria: September 11, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: SHSYXY-T-LBL-VEN-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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