Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

Institute of Hematology & Blood Diseases Hospital, China

Status

Not yet enrolling

Conditions

Ph+ ALL

Treatments

Drug: Olverembatinib

Drug: Chemotherapy Backbone Regimens

Other: CAR-T Cell Therapy

Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Drug: Venetoclax

Drug: Blinatumomab

Study type

Interventional

Funder types

Other

Identifiers

NCT07493161

IIT2026022

Details and patient eligibility

About

This is a prospective, open-label, randomized controlled trial to evaluate the efficacy and safety of low-intensity chemotherapy combined with targeted agents (venetoclax and blinatumomab) in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Patients will be randomized to receive or not receive venetoclax during the first three cycles of induction and consolidation therapy. All patients receive olverembatinib (a third-generation TKI) continuously and may receive up to 4 cycles of blinatumomab starting from the fourth cycle. The primary endpoint is the rate of BCR::ABL1 ≤0.01% at 90 days and event-free survival (EFS). Secondary endpoints include overall survival (OS), relapse-free survival (RFS), molecular relapse rate, MRD negativity rate by NGS, and cardiovascular events.

Full description

Background: Ph+ ALL is a high-risk subtype of adult ALL. Although outcomes have improved with TKI-based therapy, achieving early deep molecular response remains critical for long-term survival. Novel combinations with BCL2 inhibitor venetoclax and CD3-CD19 bispecific antibody blinatumomab may further deepen responses.

Objective: To determine whether adding venetoclax to a low-intensity chemotherapy backbone (vincristine, prednisone, olverembatinib) improves early molecular response and survival, and to explore the impact of different cycles of blinatumomab.

Design: This is a single-center, open-label, randomized controlled trial. Eligible patients are newly diagnosed Ph+ ALL aged ≥14 years, with ECOG ≤2 and adequate organ function. Patients will be randomized 1:1 to Arm A (control) or Arm B (venetoclax) during the first three cycles.

Enrollment

100 estimated patients

Sex

All

Ages

14+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Newly diagnosed ALL with t(9;22)(q34;q11) or BCR::ABL1 positivity (by PCR or FISH).
Age ≥ 14 years.
ECOG performance status ≤ 2.
Adequate organ function: Total bilirubin <1.5x ULN; AST/ALT ≤2.5x ULN; Serum creatinine <2x ULN; Cardiac enzymes <2x ULN; Serum amylase ≤1.5x ULN; Left ventricular ejection fraction (LVEF) >45%.
Male and female patients of childbearing potential must agree to use effective contraception.
Signed informed consent.

Exclusion criteria

Diagnosis of chronic myeloid leukemia in chronic, accelerated, or blast phase.
Prior systemic anti-leukemic therapy for ALL (except corticosteroids or hydroxyurea for cytoreduction prior to enrollment).
Myocardial infarction within 12 months prior to enrollment; uncontrolled/unstable angina, congestive heart failure, uncontrolled hypertension or arrhythmia.
Uncontrolled active severe infection.
Active psychiatric illness that may hinder treatment completion or informed consent.
Any other condition deemed unsuitable for the study by the investigator.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

100 participants in 2 patient groups

Standard Therapy (Chemotherapy + Olverembatinib)

Active Comparator group

Description:

Patients receive a backbone of low-intensity chemotherapy combined with olverembatinib(OVB) . Induction : Vincristine D1,8,15,22; Prednisone D1-28; Olverembatinib D1-28； Consolidation 1 \& 2: Olverembatinib D1-28; Prednisone D1-14；Vincristine D1,8. OVB dose is reduced to 20mg every other day for patients achieving CMR after Consolidation 1. Subsequent Chemotherapy: Includes High-Dose Methotrexate (cycles 4, 6, and 8 )and Intermediate-Dose Cytarabine( cycles 5, 7, and 9) with dosing adjusted based on age . Maintenance therapy: MM and VP regimen with or without venetoclax according to the study groups for 2 years. OVB maintenance therapy continues for at least 5 years. Optional Add-on: Patients may receive 1-4 cycles of blinatumomab starting after Consolidation 1.If the patient undergoes CAR-T therapy, the following conditioning regimen will be administered in cycle 4. Allogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.

Treatment:

Drug: Blinatumomab

Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Other: CAR-T Cell Therapy

Drug: Chemotherapy Backbone Regimens

Drug: Olverembatinib

Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Experimental group

Description:

Patients receive the same backbone as the Control Arm plus the BCL2 inhibitor venetoclax for the first three treatment blocks. Consolidation 1 \& 2 (OP, 4 weeks each): Olverembatinib (40mg every other day) D1-28; Prednisone D1-14；Vincristine (VCR) D1,8. OVB dose is reduced to 20mg every other day for patients achieving CMR after Consolidation 1. Subsequent Chemotherapy: Includes High-Dose Methotrexate (cycles 4, 6, and 8 )and Intermediate-Dose Cytarabine( cycles 5, 7, and 9) with dosing adjusted based on age. Maintenance therapy:MM and VP regimen with or without venetoclax according to the study groups for 2 years. Olverembatinib therapy for at least 5 years. Optional Add-on: Patients with financial means may receive 1-4 cycles of blinatumomab starting after Consolidation 1.If the patient undergoes CAR-T therapy, the following conditioning regimen will be administered in cycle 4. Allogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.

Treatment:

Drug: Blinatumomab

Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Other: CAR-T Cell Therapy

Drug: Venetoclax

Drug: Chemotherapy Backbone Regimens

Drug: Olverembatinib