Low-intensity chemotherapy with olverembatinib, venetoclax and blinatumomab for newly diagnosed Philadelphia chromosome–positive ALL

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

This trial will test whether adding venetoclax to a low‑intensity chemotherapy plan together with continuous olverembatinib and planned blinatumomab helps people aged 14+ with newly diagnosed Ph+ ALL get deeper early molecular remission and live longer.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 110 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: blinatumomab, olverembatinib, chemotherapy, prednisone
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07493161 on ClinicalTrials.gov

What this trial studies

This is a single-center, open‑label, randomized 1:1 trial for patients ≥14 years with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia and adequate organ function. All participants receive continuous olverembatinib and a low‑intensity chemotherapy backbone (vincristine and prednisone), with randomization to receive or not receive venetoclax during the first three induction/consolidation cycles; up to four cycles of blinatumomab may begin from cycle four and allo‑HSCT is allowed per physician decision. The co‑primary endpoints are the proportion of patients achieving BCR::ABL1 ≤0.01% at 90 days and event‑free survival, and secondary endpoints include overall survival, relapse‑free survival, molecular relapse rate, NGS MRD negativity, and cardiovascular events. The trial excludes patients with significant recent cardiac events, uncontrolled infection, prior systemic anti‑leukemic therapy (except limited cytoreduction), or other medical/psychiatric conditions that would prevent protocol therapy.

Who should consider this trial

Good fit: Ideal candidates are people aged 14 or older with newly diagnosed Ph+ ALL (BCR::ABL1 positive), ECOG ≤2, adequate organ function, and no prior systemic anti‑leukemic therapy besides brief cytoreduction.

Not a fit: Patients with recent myocardial infarction, uncontrolled cardiac disease, uncontrolled severe infection, a diagnosis of CML in blast/accelerated phase, or those unable to tolerate the required therapies are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could produce earlier and deeper molecular remissions and improve event‑free and overall survival while using a lower‑intensity chemotherapy backbone.

How similar studies have performed: Combining TKIs with blinatumomab or adding venetoclax has shown promising early signals in limited series and nonrandomized reports, but randomized evidence specifically in Ph+ ALL remains limited.

Eligibility criteria

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Hui Wei, MD

Conditions Ph+ ALL