Treatment plan for newly diagnosed pediatric Philadelphia chromosome–positive B‑cell acute lymphoblastic leukemia

A Phase 3, Multicenter Trial for Pediatric Philadelphia Chromosome-positive B-Acute Lymphoblastic Leukemia -2025 Project

This Phase 3 effort tests a chemotherapy‑light approach using olverembatinib together with blinatumomab and intermittent venetoclax to see if children and adolescents newly diagnosed with Ph+ B‑ALL can be cured with less toxicity.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 1 Month to 18 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: chemotherapy, blinatumomab, olverembatinib, dasatinib, Cyclophosphamide, Prednisone
• Locations: 24 sites (Hefei, Anhui and 23 other locations)
• Trial ID: NCT07152041 on ClinicalTrials.gov

What this trial studies

This protocol replaces dasatinib with the third‑generation TKI olverembatinib and pairs it with a short vincristine/prednisone lead‑in followed by a 28‑day blinatumomab induction. Consolidation includes high‑dose methotrexate with blinatumomab cycles and reduced‑dose cytarabine, while cyclophosphamide and asparaginase are omitted to reduce toxicity. Early maintenance alternates dexamethasone/vincristine plus either venetoclax or daunorubicin for five cycles after MTX and 6‑MP, and the plan includes serial MRD monitoring by IgH NGS and parallel CSF/peripheral blood olverembatinib level checks. The multicenter Phase 3 protocol enrolls children and adolescents (older than 1 month to under 18 years) at participating hospitals in China.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed patients age >1 month to <18 years with Philadelphia chromosome–positive or BCR::ABL1‑positive B‑ALL who meet standard organ‑function and consent requirements.

Not a fit: Patients who evolved from CML, have significant organ dysfunction, congenital immunodeficiency, uncontrolled infections, gastrointestinal absorption problems, or who received prolonged prior targeted therapy/chemotherapy are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could maintain or improve cure rates while substantially lowering short‑ and long‑term chemotherapy toxicity for children with Ph+ B‑ALL.

How similar studies have performed: Components of this regimen—TKI plus blinatumomab and venetoclax combos—have shown promise in Ph+ and relapsed ALL settings, but the exact olverembatinib/blinatumomab/venetoclax chemotherapy‑sparing combination in newly diagnosed pediatric Ph+ ALL is novel.

Eligibility criteria

Inclusion Criteria:

Must meet all items below:

1. Age older than 1 month to younger 18 years.
2. Newly diagnosed Philadelphia chromosome-positive or BCR::ABL1-positive B-ALL.
3. Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations.

Exclusion Criteria:

Should be excluded if had any item below:

1. ALL evolved from CML.
2. Known underlying congenital immunodeficiency or metabolic disease.
3. Congenital heart disease with cardiac insufficiency.
4. Gastrointestinal dysfunction or gastrointestinal diseases that may significantly alter the absorption of study drug.
5. Severe malnutrition, uncontrolled active infections, or serious cardiovascular diseases.
6. Subjects with significant CNS disorder (e.g., uncontrolled seizure disorder, autoimmune disease involving CNS).
7. Treated with glucocorticoids for ≥14 days, or targeted inhibitor for \> 7 days within one month before enrollment, or any chemotherapy or any systemic anticancer therapy (including but not limited to any TKI) or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression).
8. Any significant comorbidities or psychiatric disorders that may impact patient safety, compliance, informed consent, study participation, follow-up, or the interpretation of study results. In such cases, all participating sites must report directly to the PI to determine whether the patient meets exclusion criteria.

Where this trial is running

Hefei, Anhui and 23 other locations

• Anhui Medical University Second Affiliated Hospita — Hefei, Anhui, China (NOT_YET_RECRUITING)
• Chongqing Medical University Affiliated Children's Hospital — Chongqing, Chongqing Municipality, China (NOT_YET_RECRUITING)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (NOT_YET_RECRUITING)
• Guangzhou Women and Children's Medical Center — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• Nanfang Hospital, Southern Medical University — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (NOT_YET_RECRUITING)
• Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (NOT_YET_RECRUITING)
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (NOT_YET_RECRUITING)
• Wuhan Children's Hospital — Wuhan, Hubei, China (NOT_YET_RECRUITING)
• Hunan Children's Hospital — Changsha, Hunan, China (NOT_YET_RECRUITING)
• The Third Xiangya Hospital of the Central South University — Changsha, Hunan, China (NOT_YET_RECRUITING)
• Nanjing Children's Hospital Affiliated to Nanjing Medical University — Nanjin, Jiangsu, China (NOT_YET_RECRUITING)
• Children's Hospital of Soochow University — Suzhou, Jiangsu, China (NOT_YET_RECRUITING)
• Jiangxi Provincial Children's Hospital — Nanchang, Jiangxi, China (NOT_YET_RECRUITING)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (NOT_YET_RECRUITING)
• Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (NOT_YET_RECRUITING)
• Children's Hospital of Fudan University — Shanghai, Shanghai Municipality, China (NOT_YET_RECRUITING)
• Shanghai Children's Hospital — Shanghai, Shanghai Municipality, China (NOT_YET_RECRUITING)
• Shenzhen Children's Hospital — Shenzhen, Shenzhen, China (NOT_YET_RECRUITING)
• West China Second University Hospita — Chengdu, Sichuan, China (NOT_YET_RECRUITING)
• Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC — Tianjin, Tianjin Municipality, China (RECRUITING)
• Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC — Tianjin, Tianjin Municipality, China (NOT_YET_RECRUITING)
• Hong Kong Children's Hospital, The Chinese University of Hong Kong — Hong Kong, Hong Kong (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Xiaofan Zhu, MD — Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
• Study coordinator: Jingliao Zhang, MD

Conditions: Acute Lymphoblastic Leukemia Philadelphia Chromosome-positive, Childhood Leukemia, Acute Lymphoblastic, olverembatinib, Blinatumomab, venetoclax