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.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.
  • 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.

Study Details

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.

Key Dates

Start date
Apr 10, 2026
Status verified
May 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 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.
  • 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.

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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