A Phase I Study of Venetoclax to Augment Epigenetic Modification and Chemotherapy in Pediatric and Young Adult Patients With Relapsed and Refractory Acute Myeloid Leukemia
Medical College of Wisconsin
Summary
The investigator is testing the addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy to enhance treatment response in AML patients.
Description
The investigators are testing if the addition of venetoclax to epigenetic therapy will not only enhance the treatment response for patients with epigenetic lesions but improve the poor response we have observed in those patients without epigenetic lesions. The addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy will be investigated. This regimen may be tolerable and increase LSC targeting resulting in deeper, more durable responses in children, adolescents, and young adults with relapsed or refractory AML The study will enroll patients in two strata - a pr…
Eligibility
- Age range
- 1–25 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria * Diagnosis 1. Patients with AML must have measurable disease (≥M1 marrow) in the bone marrow. * 1st or greater relapse, OR * Failed to go into remission after 1st or greater relapse, OR * Failed to go into remission from original diagnosis after 2 or more induction attempts 2. Patients may have CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy. 3. Patients with treatment related AML (tAML) are eligible. A relapse of tAML is not necessary to enroll on this study thus newly diagnosed tAML are el…
Interventions
- DrugVenetoclax
Dose Level 0: Day 1 60 mg/m2 PO x1, Days 2-14 120 mg/m2/dose PO once daily (Max: 200 mg/day) Dose level 1: Day 1 120 mg/m2 PO x1, Days 2-14 240 mg/m2/dose PO once daily (Max: 400 mg/day) Dose level 2: Day 1 180 mg/m2 PO x1, Days 2-14 360 mg/m2/dose PO once daily (Max: 600 mg/day)
- DrugAzacitadine
75 mg/m2/dose IV once daily over 15 minutes
- DrugVorinostat
1 year to 17.99 years old: 180 mg/m2/dose PO once daily ≥18 years old 200 mg PO BID. Doses should be separated by 12 hr (±4 hr)
- DrugCytarabine
2000 mg/m2/dose IV once daily over 3 hours IT Cytarabine: 1. \- 1.99 years old: 30 mg 2. \- 2.99 years old: 50 mg * 3 years old: 70 mg
- DrugFludarabine
30 mg/m2/dose IV once daily over 30 minutes
- DrugFilgrastim
5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily
Location
- Children's WisconsinMilwaukee, Wisconsin