NCT05317403

Venetoclax to Augment Epigenetic Modification and Chemotherapy

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 1 Year – 25 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 primary stratum of eligible patients without Down syndrome, and a secondary stratum of eligible patients with Down syndrome (DS-AML). Subjects will receive two 35 day cycles of therapy.

Conditions

• Acute Myeloid Leukemia, in Relapse
• Acute Myeloid Leukemia Refractory

Interventions

Type	Name	Description
DRUG	Venetoclax	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)
DRUG	Azacitadine	75 mg/m2/dose IV once daily over 15 minutes
DRUG	Vorinostat	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)
DRUG	Cytarabine	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
DRUG	Fludarabine	30 mg/m2/dose IV once daily over 30 minutes
DRUG	Filgrastim	5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily

Timeline

• Start date: 2023-03-31
• Primary completion: 2027-01-01
• Completion: 2027-01-01
• First posted: 2022-04-07
• Last updated: 2026-01-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study