drugset
drugset / Trial / NCT05192889

Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax

NCT05192889 ↗

Phase 1/2 Active not recruiting 35 enrolled St. Jude Children's Research Hospital AbbVie · collab
Non-randomizedSequentialOpen-labelTreatment

Summary

This is a phase I/II clinical trial evaluating the activity of combination chemotherapy with venetoclax and navitoclax in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) and assessing the combination dose of venetoclax combinations with either blinatumomab for CD19-positive patients or navitoclax and high-dose cytarabine for CD19-negative patients. Primary Objectives * To compare Minimal Residual Disease (MRD)-negative CR/CRi rate in children with relapsed or refractory acute lymphoblastic leukemia or lymphoma (rALL) following Block 1 therapy with venetoclax and navitoclax based reinduction to historical controls. * To identify the recommended phase 2 combination dose (RP2D) of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. Secondary Objectives * To estimate the tolerability and activity of venetoclax based consolidation in novel combinations with a) high-dose cytarabine and navitoclax or b) blinatumomab. * To describe event-free and overall survival in patients treated with this regimen. Exploratory Objectives * To evaluate MRD-negative CR/CRi rates in each prespecified groups: late first relapse B-ALL; early first relapse and second or greater relapse B-ALL; and relapsed T-ALL. * To identify drug sensitivity patterns in patient samples prior to and after receiving combination therapy and evaluate mechanisms of disease resistance/ escape. * To explore immune subsets during and after this regimen. * Evaluate response to therapy in rare relapse patient subsets. * Explore breakthrough infections in children and young adults with relapsed or refractory ALL

Timeline

Start
2022-08-25
Primary completion
2024-06-13
Completion
2027-02

Drugs

EvaluationDrugModalityDoseRoute
Subject Blinatumomab Monoclonal antibody 5 ug/m2 Intravenous
Subject Blinatumomab Monoclonal antibody 9 ug Intravenous
Subject Blinatumomab Monoclonal antibody 15 ug/m2 Intravenous
Subject Blinatumomab Monoclonal antibody 28 ug Intravenous
Subject Cytarabine Small molecule 36 mg Intravenous
Subject Cytarabine Small molecule 50 mg/m2 Intravenous
Subject Cytarabine Small molecule 1000 mg/m2 Intravenous
Subject Cytarabine Small molecule 1500 mg/m2 Intravenous
Subject Cytarabine Small molecule 3000 mg/m2 Intravenous
Subject Navitoclax Small molecule 25 mg Oral
Subject Navitoclax Small molecule 50 mg Oral
Subject Venetoclax Small molecule 120 mg/m2 Oral
Subject Venetoclax Small molecule 240 mg/m2 Oral
Background Asparaginase Erwinia chrysanthemi Protein / enzyme biologic — Intravenous
Background Calaspargase Pegol Protein / enzyme biologic 1000 iu Intravenous
Background Calaspargase Pegol Protein / enzyme biologic 2500 iu Intravenous
Background Cyclophosphamide Other / unclassified 300 mg/m2 Intravenous
Background Dexamethasone Small molecule 3 mg/m2 Oral
Background Dexamethasone Small molecule 5 mg/m2 Oral
Background Dexamethasone Small molecule 6 mg/m2 Oral
Background Dexamethasone Small molecule 10 mg/m2 Oral
Background Etoposide Small molecule 150 mg/m2 Intravenous
Background Hydrocortisone Other / unclassified 24 mg Intrathecal
Background Leucovorin Small molecule 5 mg Oral
Background Leucovorin Small molecule 15 mg Oral
Background MERCAPTOPURINE ANHYDROUS Small molecule 50 mg/m2 Oral
Background MERCAPTOPURINE ANHYDROUS Small molecule 60 mg/m2 Oral
Background MERCAPTOPURINE ANHYDROUS Small molecule 75 mg/m2 Oral
Background Methotrexate Small molecule 12 mg Intravenous
Background Methotrexate Small molecule 20 mg/m2 Intravenous
Background Methotrexate Small molecule 5000 mg/m2 Intravenous
Background Pegaspargase Protein / enzyme biologic 2500 iu Intravenous
Background Vincristine Small molecule 1.5 mg/m2 Intravenous
Background dasatinib anhydrous Small molecule 80 mg/m2 Oral

Indications

acute lymphoblastic leukemia