Newly-diagnosed Pediatric Ph-positive B-ALL Protocol (CAMS-Ph+ B-ALL)

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Enrolling; Phase 3

Conditions: Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+); Childhood Leukemia, Acute Lymphoblastic

Treatments: Drug: olverembatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT07152041

IIT2025041

Details and patient eligibility

About

This prospective clinical trial evaluates the effectiveness and safety of "chemotherapy-light" regimen incorporating the third-generation TKI olverembatinib, the bi-specific CD3/CD19 T cell engager blinatumomab, and the BCL-2 selective inhibitor venetoclax for newly diagnosed pediatric/adolescent patients with Ph+ ALL. The CCCG-Ph+ B-ALL-2025 protocol will be modified as following compared to the CCCG-ALL-2020 protocol

Full description

1. All Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen.
2. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol.
3. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity.
4. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase.
5. To decrease the toxicities of high-dose AraC, the dosage will be reduced to 1 g/m2 in the consolidation 2 phase in contrast to 2 g/m2 in 2020 protocol.
6. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP.
7. Cyclophosphamide and asparaginase are totally omitted from the entire treatment to mitigate toxicities.
8. Olverembatinib concentrations are recommended to be examined (cerebrospinal fluid and peripheral blood in parallel) before OVB given, after full dosing of OVB, and/or Blina+OVB, best to match lumbar puncture assessments timepoints.
9. IgH rearrangement by NGS MRD will be added as an evaluation indicator, with testing frequency matching bone marrow aspiration assessments.
10. Pharmarcotyping studies are recommended at baseline if condition permits.
11. For patients who cannot use full-dose blinatumomab, we will adopt the CCCG-Ph+ALL2020 protocol. complications.

Enrollment: 150 estimated patients

Sex: All

Ages: 1 month to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

150 participants in 1 patient group

OVB+Blina+VEN+Chemo-light regimen

Experimental group

Description:

All Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen. Cyclophosphamide and asparaginase are totally omitted from the entire treatment to mitigate toxicities. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase. The dosage of AraC will be reduced to 1 g/m2 in the consolidation 2 phase. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP.

Treatment:

Drug: olverembatinib