Acute Myeloid Leukemia, in RelapsePhase 1NCT05317403
Venetoclax to Augment Epigenetic Modification and Chemotherapy
A Phase 1 study testing Venetoclax, Azacitadine and Vorinostat in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia Refractory, run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory
- What is being tested?
- Venetoclax, Azacitadine and Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2023to Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis
- 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
- Patients may have CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
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- 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.
- Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. This includes flotetuzumab.
- Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (i.e. Gemtuzumab = 36 days)
- Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines or CAR-T cells.
- XRT: Craniospinal XRT is prohibited during protocol therapy. No waiting period is necessary for radiation given to non-CNS chloromas; ≥ 90 days must have elapsed if prior TBI or craniospinal XRT.
- Infection Prevention: Patients must be able to tolerate and receive anti-fungal prophylaxis with echinocandins or amphotericin therapy for the duration of their treatment course and neutrophil recovery (post-nadir ANC is > 750/μL).
- Inhibitors and Inducers ofCYP3A4
- Patients taking strong CYP3A4 inhibitors should have their venetoclax dose reduced by 75%
- Patients taking moderate CYP3A4 inhibitors should have their venetoclax dose reduced by 50%
- Inhibitors of P-glycoprotein (P-gp): Patients taking p-glycoprotein inhibitors should have their venetoclax doses reduced by 50%.
- Renal and hepatic function- Patients must have adequate renal and hepatic functions as indicated by the following laboratory values:
- Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine
- Adequate Liver Function Defined as: Direct bilirubin < 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) < 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia. This must be reviewed by and approved by the study chair or vice chair.
- Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% OR ejection fraction of ≥ 50%.
- Reproductive Function
- Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
- Informed Consent- Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks, and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age-appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.
- Protocol Approval- All institutional, FDA, and OHRP requirements for human studies must be met.
Who cannot join
- •.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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Wisconsin
Milwaukee, Wisconsin, 53226
Amberley Kemic, RN, 414-266-2038 ext. 2038, akemic@childrenswi.org
MACCcto@mcw.edu
About this study
Official title: 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
The investigator is testing the addition of venetoclax to 5-azacitidine and vorinostat followed by standard chemotherapy to enhance treatment response in AML patients.
Read the 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.
- Being tested
- Venetoclax, Azacitadine, Vorinostat, Cytarabine, Fludarabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
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)
AzacitadineDrug
75 mg/m2/dose IV once daily over 15 minutes
VorinostatDrug
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)
CytarabineDrug
2000 mg/m2/dose IV once daily over 3 hours
IT Cytarabine:
- - 1.99 years old: 30 mg
- - 2.99 years old: 50 mg
- 3 years old: 70 mg
FludarabineDrug
30 mg/m2/dose IV once daily over 30 minutes
FilgrastimDrug
5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Venetoclax; Drug: Azacitadine; Drug: Vorinostat; Drug: Cytarabine; Drug: Fludarabine; Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 42 months
Secondary outcomes (6)
Response Rates
Response rates as measured by morphologic response (CR)
Measured: 42 months
Response Rates
Response rates as measured by morphologic response (PD)
Measured: 42 months
Response Rates
Response rates as measured by morphologic response (SD)
Measured: 42 months
Response Rates
Response rates as measured by morphologic response (CRi)
Measured: 42 months
Response Rates
Response rates as measured by morphologic response (PR)
Measured: 42 months
MRD
minimal residual disease (MRD) via multiparameter flow cytometry
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start31 Mar 2023
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia, in RelapseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Burke, Medical College of Wisconsin
- Investigators
- Michael Burke, MD, Study chair, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05317403
- Sponsor's protocol ID
- Venetoclax Epigenetic
- Status last verified
- Jan 2026
- First submitted
- 8 Mar 2022
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05317403
- Acronym / sponsor ID
- Venetoclax Epigenetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 31 Mar 2023 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 7 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AML without Down Syndrome | Other | Drug: Venetoclax, Drug: Azacitadine, Drug: Vorinostat, Drug: Cytarabine, Drug: Fludarabine, Drug: FilgrastimThe 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 |
| AML with Down Syndrome | Other | Drug: Venetoclax, Drug: Azacitadine, Drug: Vorinostat, Drug: Cytarabine, Drug: Fludarabine, Drug: FilgrastimThe 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 |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (35 listed)
- Diagnosis
- 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.
- Renal and hepatic function- Patients must have adequate renal and hepatic functions as indicated by the following laboratory values:
- Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% OR ejection fraction of ≥ 50%.
Key exclusion criteria (6 listed)
- •.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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VenetoclaxDose 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 | AML with Down Syndrome, AML without Down Syndrome |
| Azacitadine75 mg/m2/dose IV once daily over 15 minutes | Drug | AML with Down Syndrome, AML without Down Syndrome |
| Vorinostat1 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 | AML with Down Syndrome, AML without Down Syndrome |
| Cytarabine2000 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 | AML with Down Syndrome, AML without Down Syndrome |
| Fludarabine30 mg/m2/dose IV once daily over 30 minutes | Drug | AML with Down Syndrome, AML without Down Syndrome |
| Filgrastim5 microgram/kg/dose subcutaneous (or IV over 15-30 min) once daily | Drug | AML with Down Syndrome, AML without Down Syndrome |
Primary outcome
Venetoclax Dose-Limiting Toxicity
Time frame: 42 months
The primary endpoint, for dose escalation of venetoclax, is the occurrence of a dose-limiting toxicity (DLT) observed during the first course of therapy.
6 secondary outcomes
Response Rates
Time frame: 42 months
Response Rates
Time frame: 42 months
Response Rates
Time frame: 42 months
Response Rates
Time frame: 42 months
Response Rates
Time frame: 42 months
MRD
Time frame: 42 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Burke, MD study chair
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Venetoclax, Azacitadine and Vorinostat in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia Refractory, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amberley Kemic, RN (414-266-2038, akemic@chw.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venetoclax Dose-Limiting Toxicity (time frame: 42 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026; AzTrials last refreshed its copy on 6 Nov 2026.