Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical Trial

Official title:

Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05660473
• Other study ID #: IIT2022052-EC-1
• Status: Recruiting
• Phase: Phase 2
• Start date: October 31, 2022
• Est. completion date: December 30, 2027

Study information

• Verified date: December 2022
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Jianxiang Wang, Dr
• Phone: 86-22-23909120
• Email: wangjx[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The pediatric-inspired regimen has greatly improved the prognosis of adult patients with with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), but relapse remains a great challenge. Venetoclax (Ven) is an oral, selective inhibitor of B-cell lymphoma 2 (Bcl-2). Although this drug is currently used primarily for acute myeloid leukemia, in vitro as well as small cohort studies suggest a effect in acute lymphoblastic leukemia. This study proposes to combine pediatric-inspired regimen with venetoclax for the treatment of adult patients with Ph- ALL, aiming to improve the MRD-negative complete remission rate measured by flow cytometry after induction and to reduce relapse, thus further improving patients overall survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 30, 2027
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

Inclusion Criteria:

• De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification

• Age: 14 -60 years

• Male or female

• 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

Exclusion Criteria:

• Burkitt lymphoma/leukemia

• Acute Leukemia of Ambiguous Lineage

• Female patients who are pregnant or breast feeding

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

• History of pancreatitis

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

• History of active gastrointestinal bleeding within the last 6 months

• History of arterial/venous thrombosis within the last 6 months

• Known HIV seropositivity

• 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
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Respiratory Aspiration

Intervention

Drug:
• Vincristine
Anti-tumor alkaloids
• Daunorubicin
Anthracycline
• Cyclophosphamide
Alkylating agent
• Pegaspargase
Polyethylene glycol (PEG) conjugated to L-asparaginase
• Prednisone
Glucocorticoids
• Cytarabine
Pyrimidine antimetabolites
• 6-mercaptopurine
Cell cycle-specific antitumor drug
• Dexamethasone
Glucocorticoids
• Methotrexate
Antifolate antineoplastic drug
• Venetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRD-negative complete remission rate measured by flow cytometry		After induction (4 week)
Secondary	Complete remission (CR) rate		After 2 cycles of chemotherapy, an expected average of 3 months
Secondary	Overall survival (OS)	From the date of registration to the date of death resulting from any cause	Up to 5 years post-registration
Secondary	Relapse free survival (RFS)	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 5 years post-registration
Secondary	Disease-free Survival (DFS)	From CR1 to relapse, death from any cause or last follow-up	Up to 5 years post-registration
Secondary	The rate of adverse events		An expected average of 24 months