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

NCT05594784 | Completed Phase 2

• 1 other identifier: IIT2022040
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• CMR rate

  Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days)

  At 3 months of treatment (90 days)

Secondary Outcomes (6)

• Overall survival(OS)

  up to 60 months

• Relapse free survival

  up to 60 months

• The rate of adverse events

  an expected average of 24 months

• complete remission (CR) rate

  an expected average of 3 months

• The duration of CR

  up to 60 months

Study Arms (1)

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

EXPERIMENTAL

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.

Drug: Olverembatinib; Drug: Venetoclax; Drug: prednisone; Drug: Vincristine

Interventions

Olverembatinib DRUG

a third-generation TKI

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

Venetoclax DRUG

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

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

prednisone DRUG

Glucocorticoids

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

Vincristine DRUG

Anti-tumor alkaloids

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 14 years or older
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
• 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%;
• Subject has provided written informed consent prior to any screening procedure

You may not qualify if:

• Lymphoid blast crisis of chronic myelocytic leukemia (CML)
• Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
• Clinical manifestations of CNS or extramedullary involvement with ALL
• 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.)
• Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
• Known HIV seropositivity
• History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
• Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL)
• Female patients who are pregnant or breast feeding
• Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of \>7.5%. Patients with preexisting, well-controlled diabetes are not excluded
• Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, 300020, China

Location

Related Publications (1)

• 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.

  PMID: 40588568 DERIVED

MeSH Terms

Interventions

olverembatinib; venetoclax; Prednisone; Vincristine

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Jianxiang Wang, Dr

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: October 26, 2022
• Study Start: October 8, 2022
• Primary Completion: March 25, 2025
• Study Completion: March 25, 2025
• Last Updated: June 3, 2025

Record last verified: 2024-05

Locations

CN (1)