Venetoclax to Augment Epigenetic Modification and Chemotherapy

NCT05317403 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Venetoclax Epigenetic
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Outcome Measures

Primary Outcomes (1)

• Venetoclax Dose-Limiting Toxicity

  The primary endpoint, for dose escalation of venetoclax, is the occurrence of a dose-limiting toxicity (DLT) observed during the first course of therapy.

  42 months

Secondary Outcomes (6)

• Response Rates

  42 months

• Response Rates

  42 months

• Response Rates

  42 months

• Response Rates

  42 months

• Response Rates

  42 months

Study Arms (2)

AML without Down Syndrome

OTHER

The subject receives 2 courses of therapy approximately 35 days each. Venetoclax: Days 1-14 Azacitidine and Vorinostat: Days 1-5 Filgrastim Days: 5 start and continue until post-nadir ANC \> 500 cells/mm3 Fludarabine and Cytarabine Days 6 - 10 IT Cytarabine Day 0 or 1, optional between day 35 and 42

Drug: Venetoclax; Drug: Azacitadine; Drug: Vorinostat; Drug: Cytarabine; Drug: Fludarabine; Drug: Filgrastim

AML with Down Syndrome

OTHER

The subject receives 2 courses of therapy approximately 35 days each. Venetoclax: Days 1-14 Azacitidine and Vorinostat: Days 1-5 Filgrastim Days: 5 start and continue until post-nadir ANC \> 500 cells/mm3 Fludarabine and Cytarabine Days 6 - 10 IT Cytarabine Day 0 or 1, optional between day 35 and 42

Drug: Venetoclax; Drug: Azacitadine; Drug: Vorinostat; Drug: Cytarabine; Drug: Fludarabine; Drug: Filgrastim

Interventions

Cytarabine DRUG

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

AML with Down Syndrome; AML without Down Syndrome

Fludarabine DRUG

30 mg/m2/dose IV once daily over 30 minutes

AML with Down Syndrome; AML without Down Syndrome

Filgrastim DRUG

5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily

AML with Down Syndrome; AML without Down Syndrome

Venetoclax DRUG

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)

AML with Down Syndrome; AML without Down Syndrome

Azacitadine DRUG

75 mg/m2/dose IV once daily over 15 minutes

AML with Down Syndrome; AML without Down Syndrome

Vorinostat DRUG

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)

AML with Down Syndrome; AML without Down Syndrome

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis
• Patients with AML must have measurable disease (≥M1 marrow) in the bone marrow.
• st 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
• Patients may have CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
• 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 eligible.
• Patients with immunophenotypic AML evolving as lineage switch from ALL or acute leukemia NOS, may be eligible if they have relapsed/refractory disease
• Patients with Down syndrome are eligible
• Performance Level- Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age. (See Appendix II for Performance Scales)
• Prior Therapy- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy
• Cytoreduction with hydroxyurea Hydroxyurea can be initiated and continued for up to 24 hours prior to the start of Venetoclax. It is recommended to use hydroxyurea in patients with significant leukocytosis (WBC \> 50,000/L) to control blast count before initiation of systemic protocol therapy.
• Patients who relapsed while they are receiving cytotoxic therapy At least 7 days must have elapsed since the completion of the cytotoxic therapy, except Intrathecal chemotherapy.
• Hematopoietic stem cell transplant: Patients who have experienced relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD), and are at least 90 days post-transplant at the time of enrollment, no longer receiving GVHD therapy.

You may not qualify if:

• .Patients will be excluded if they have a known allergy to any of the drugs used in the study.
• Patients will be excluded if they have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
• Patients will be excluded if they have had any positive fungal culture within 30 days prior to enrollment or evidence of disseminated fungal disease.
• Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder, or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
• Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Vorinostat; Cytarabine; fludarabine; Filgrastim

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Michael Burke, MD

  Medical College of Wisconsin

  STUDY CHAIR

Central Study Contacts

Amberley Kemic, RN

CONTACT

414-266-2038; akemic@chw.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Pediatrics, Division of Hematology/Oncology/BMT

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: April 7, 2022
• Study Start: March 31, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)