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Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

ConditionPh+ ALL
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age14+
SponsorInstitute of Hematology & Blood Diseases Hospital, China

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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%.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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 intervention

    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.

Treatment groups

110 Participants
are divided into 2 treatment groups
Group A: Standard Therapy (Chemotherapy + Olverembatinib)Active comparator 5 interventions
Group B: Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
up to 90 days
2

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

Time frame
From the start of InO consolidation therapy up to 2 years

Secondary outcomes

1

Overall Survival

Time frame
up to 5 years
2

Relapse-Free Survival

Time frame
up to 5 years
3

Cumulative incidence of molecular relapse

Time frame
up to 5 years
4

Cumulative incidence of hematologic relapse

Time frame
up to 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Hematology & Blood Diseases Hospital, China

Lead sponsor

Source ClinicalTrials.gov
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