Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for de Novo Ph+ ALL

NCT ID: NCT05594784

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-08
• Study Completion Date: 2025-03-25

Brief Summary

The introduction of TKIs has greatly improved the prognosis of Ph+ ALL patients. The third-generation TKI ponatinib in combination with chemotherapy has demonstrated superior efficacy to first- and second-generation TKIs. However, unfortunately, ponatinib is not available in mainland China. Olverembatinib is the only third-generation TKI drug currently approved in mainland China. Venetoclax is an oral selective inhibitor of Bcl-2, and small exploratory clinical studies have demonstrated that venetoclax in combination with ponatinib showed high rates of CR as well as molecular response in relapsed/refractory Ph+ ALL. This study will explore the safety and efficacy of olverembatinib in combination with reduced-intensity chemotherapy and venetoclax in patients with newly diagnosed Ph+ ALL.

Conditions

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

For Induction cycle, olverembatinib will be given orally 40mg every other day. Patients with CMR, olverembatinib will be reduced to 30 mg every other day.

Induction and consolidation cycles combined with a certain period of venetoclax.

Reduced-intensity chemotherapy regimens consist mainly of vincristine and prednisone. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients who keep BCR/ABL negative can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy.

Group Type: EXPERIMENTAL

Olverembatinib

Intervention Type: DRUG

a third-generation TKI

Venetoclax

Intervention Type: DRUG

a selective inhibitor of B-cell lymphoma 2 (Bcl-2)

prednisone

Intervention Type: DRUG

Glucocorticoids

Vincristine

Intervention Type: DRUG

Anti-tumor alkaloids

Interventions

Olverembatinib

a third-generation TKI

Intervention Type: DRUG

Venetoclax

a selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Intervention Type: DRUG

prednisone

Glucocorticoids

Intervention Type: DRUG

Vincristine

Anti-tumor alkaloids

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female patients aged 14 years or older

2. Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia; Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination

3. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

4. Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%;

5. Subject has provided written informed consent prior to any screening procedure

Exclusion Criteria

1. Lymphoid blast crisis of chronic myelocytic leukemia (CML)

2. Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)

3. Clinical manifestations of CNS or extramedullary involvement with ALL

4. Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)

5. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment

6. Known HIV seropositivity

7. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis

8. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)

9. Female patients who are pregnant or breast feeding

10. Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded

11. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jianxiang Wang, Dr

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

Institute of Hematology & Blood Diseases Hospital

Tianjin, , China

Countries

China

References

Gong X, Liu W, Liu Y, Fang Q, Gu R, Liu K, Lin D, Zhou C, Zhang G, Gong B, Wei S, Li Y, Li S, Wang Y, Hu Y, Qiu S, Liu B, Wang Y, Mi Y, Wei H, Wang J. Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial. Leukemia. 2025 Aug;39(8):1838-1847. doi: 10.1038/s41375-025-02674-8. Epub 2025 Jun 30.

Reference Type: DERIVED

PMID: 40588568 (View on PubMed)

Other Identifiers

IIT2022040

Identifier Type: -

Identifier Source: org_study_id