Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

NCT07493161 | Recruiting

• 1 other identifier: IIT2026022
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, prospective clinical cohort study evaluating the efficacy and safety of reduced-intensity chemotherapy combined with targeted therapy and immunotherapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study consists of two integrated parts. The first part is a randomized controlled comparison to investigate the role of venetoclax, a BCL2 inhibitor, when added to a backbone of olverembatinib (a third-generation TKI) and reduced-intensity chemotherapy (VPVO regimen) during the first three cycles of induction/consolidation therapy. The second part is a single-arm exploration of inotuzumab ozogamicin (InO) combined with TKI and chemotherapy as a consolidation strategy for patients who complete the 90-day primary endpoint assessment but do not receive blinatumomab, offering an alternative to blinatumomab-based regimens. The primary endpoint for the venetoclax part is the rate of BCR-ABL \< 0.01% at day 90. The primary endpoint for the InO consolidation part is modified event-free survival (EFS) from the start of InO treatment. Key secondary endpoints include overall survival (OS), relapse-free survival (RFS), cumulative incidence of molecular and hematologic relapse, NGS MRD negativity rates, and safety profiles including cardiovascular events and SOS/VOD. The study aims to enroll 110 patients in the initial phase and an additional 78 patients for the InO consolidation phase.

Conditions

Ph+ ALL

Outcome Measures

Primary Outcomes (2)

• Rate of BCR::ABL1 ≤0.01% at 90 days (after three cycles of treatment)

  up to 90 days

• Modified Event-Free Survival (mEFS) from start of InO consolidation

  From the start of InO consolidation therapy up to 2 years

Secondary Outcomes (10)

• 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

Study Arms (2)

Standard Therapy (Chemotherapy + Olverembatinib)

ACTIVE COMPARATOR

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 for 2 years. OVB maintenance therapy continues for at least 5 years. Optional Add-on 1: Patients may receive 1-4 cycles of blinatumomab starting from Cycle 4. Optional Add-on 2: Patients who do not receive blinatumomab will receive inotuzumab ozogamicin (InO) starting from Cycle 4 Allogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.

Drug: Olverembatinib; Drug: Blinatumomab; Drug: Chemotherapy Backbone Regimens; Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Drug: Inotuzumab ozogamicin

Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

EXPERIMENTAL

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 venetoclax for 2 years. Olverembatinib therapy for at least 5 years. Optional Add-on 1: Patients with financial means may receive 1-4 cycles of blinatumomab starting from Cycle 4. Optional Add-on 2: Patients who do not receive blinatumomab will receive inotuzumab ozogamicin (InO) starting from Cycle 4. Allogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.

Drug: Olverembatinib; Drug: Venetoclax; Drug: Blinatumomab; Drug: Chemotherapy Backbone Regimens; Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Drug: Inotuzumab ozogamicin

Interventions

Inotuzumab ozogamicin DRUG

Optional add-on therapy 2. Start from 4 cycle. at a total dose of 2 mg per cycle. TKI should be discontinued 5 days prior to InO administration, and olverembatinib oral therapy should be resumed one week after InO administration. For patients who remain NGS MRD-positive after one cycle of InO, a repeat cycle of InO may be considered. Note: If 2 cycles given,cycle 9 are omitted.

Standard Therapy (Chemotherapy + Olverembatinib); Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Venetoclax DRUG

BCL-2 inhibitor. Used only in the experimental arm.Induction: Ramp-up: 100mg D1, 200mg D2, 400mg D3-28. Consolidation: 400mg D1-7.

Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Blinatumomab DRUG

CD19/CD3 bispecific T-cell engager (BiTE). Optional add-on therapy 1.Start from 4 cycle. Duration: 1-4 cycles (each cycle = 28 days), intercalated with chemotherapy cycles. Note: If ≥3 cycles given,cycle 8 and 9 are omitted.

Standard Therapy (Chemotherapy + Olverembatinib); Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Olverembatinib DRUG

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.

Standard Therapy (Chemotherapy + Olverembatinib); Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) OTHER

Recommended for patients with MRD ≥0.01% after two treatment blocks.

Standard Therapy (Chemotherapy + Olverembatinib); Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Chemotherapy Backbone Regimens DRUG

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.

Standard Therapy (Chemotherapy + Olverembatinib); Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Interventions

olverembatinib; venetoclax; blinatumomab; Inotuzumab Ozogamicin

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2026
• First Posted: March 25, 2026
• Study Start: April 10, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 30, 2030
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)