Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Study ID
NCT07493161
Status
Recruiting
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Conditions

  • Ph+ ALL

Eligibility Criteria

Sex
ALL
Age
14 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • 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.
  • 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.
  • 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.
  • 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.
  • Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) — OTHER
    Recommended for patients with MRD ≥0.01% after two treatment blocks.
  • 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.

Study Details

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.

Key Dates

First listed
Mar 25, 2026
Start date
Apr 10, 2026
Status verified
Jul 2026
Primary completion
Mar 31, 2028
Completion
Mar 30, 2030

Study Design

Enrollment
110 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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 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.
  • 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 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.

Primary Outcome Measure

Rate of BCR::ABL1 ≤0.01% at 90 days (after three cycles of treatment) [ Time Frame: up to 90 days ]

Central Contacts

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