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

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for Newly Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: A Prospective, Single-arm, Single-center Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05594784
• Other study ID #: IIT2022040-EC-1
• Status: Recruiting
• Phase: Phase 2
• Start date: October 8, 2022
• Est. completion date: March 1, 2025

Study information

• Verified date: October 2023
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: Jianxiang Wang, Dr
• Phone: 86-22-23909120
• Email: wangjx[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 1, 2025
• Est. primary completion date: October 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Olverembatinib
a third-generation TKI
• Venetoclax
a selective inhibitor of B-cell lymphoma 2 (Bcl-2)
• prednisone
Glucocorticoids
• Vincristine
Anti-tumor alkaloids

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMR rate	Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days)	At 3 months of treatment (90 days)
Secondary	Overall survival(OS)	From the date of registration to the date of death resulting from any cause	up to 60 months
Secondary	Relapse free survival	From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day	up to 60 months
Secondary	The rate of adverse events		an expected average of 24 months
Secondary	complete remission (CR) rate		an expected average of 3 months
Secondary	The duration of CR		up to 60 months
Secondary	The duration of molecular CR		up to 60 months