Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

Low-intensity Chemotherapy Combined With Targeted-Immunotherapy for Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Prospective Clinical Cohort Study

This is a prospective, open-label, randomized controlled trial to evaluate the efficacy of low-intensity chemotherapy combined with 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.

Study Overview

• Status: Recruiting
• Conditions: Ph+ ALL
• Intervention / Treatment: Drug: Olverembatinib; Drug: Blinatumomab; Drug: Chemotherapy Backbone Regimens; Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Drug: Venetoclax

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Recruiting
      • Blood diseases hospital
      • Contact: hui wei, MD; Phone Number: 86-13132507161; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Therapy (Chemotherapy + Olverembatinib); 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.	Drug: Olverembatinib; Third-generation tyrosine kinase inhibitor (TKI) targeting BCR-ABL1, including T315I mutation.nduction & Consolidation: 40mg every other day. After achieving CMR: Reduced to 20mg every other day during maintenance.; Drug: Blinatumomab; CD19/CD3 bispecific T-cell engager (BiTE). Optional add-on therapy.Start: After first consolidation. Duration: 1-4 cycles (each cycle = 28 days), intercalated with chemotherapy cycles. Note: If ≥3 cycles given,cycle 8 and 9 are omitted.; Drug: Chemotherapy Backbone Regimens; Induction (VPO/VPVO): Vincristine + Prednisone + Olverembatinib (± Venetoclax). Consolidation (VOVP/OVP): Vincristine +Olverembatinib + Prednisone (± Venetoclax). HD-MTX: High-dose methotrexate with leucovorin rescue in cycle 4,6,8. ID-AraC: Intermediate-dose cytarabine in cycle 5,7,9.; Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Recommended for patients with MRD ≥0.01% after two treatment blocks.
Experimental: Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax); 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.	Drug: Olverembatinib; Third-generation tyrosine kinase inhibitor (TKI) targeting BCR-ABL1, including T315I mutation.nduction & Consolidation: 40mg every other day. After achieving CMR: Reduced to 20mg every other day during maintenance.; Drug: Blinatumomab; CD19/CD3 bispecific T-cell engager (BiTE). Optional add-on therapy.Start: After first consolidation. Duration: 1-4 cycles (each cycle = 28 days), intercalated with chemotherapy cycles. Note: If ≥3 cycles given,cycle 8 and 9 are omitted.; Drug: Chemotherapy Backbone Regimens; Induction (VPO/VPVO): Vincristine + Prednisone + Olverembatinib (± Venetoclax). Consolidation (VOVP/OVP): Vincristine +Olverembatinib + Prednisone (± Venetoclax). HD-MTX: High-dose methotrexate with leucovorin rescue in cycle 4,6,8. ID-AraC: Intermediate-dose cytarabine in cycle 5,7,9.; Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Recommended for patients with MRD ≥0.01% after two treatment blocks.; Drug: Venetoclax; BCL-2 inhibitor. Used only in the experimental arm.Induction: Ramp-up: 100mg D1, 200mg D2, 400mg D3-28. Consolidation: 400mg D1-7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-Free Survival	up to 5 years
Rate of BCR::ABL1 ≤0.01% at 90 days (after three cycles of treatment)	up to 90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	up to 5 years
Relapse-Free Survival	up to 5 years
Cumulative incidence of molecular relapse	up to 5 years
Cumulative incidence of hematologic relapse	up to 5 years
Proportion of patients with next-generation sequencing minimal residual disease <0.01% after three cycles of treatment (90 days)	up to 90 days
Proportion of patients with next-generation sequencing minimal residual disease <0.01% at the end of consolidation therapy	up to 1 year
Incidence of treatment-related cardiovascular events	up to 5 years from the initiation of treatment
Proportion of patients with BCR::ABL1 ≤0.01% at completion of consolidation therapy	up to 90 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 30, 2030

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Investigative Techniques; Therapeutics; Biological Therapy; Immunologic Techniques; Immunomodulation; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; venetoclax; blinatumomab; olverembatinib
• Other Study ID Numbers: IIT2026022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No