Acute Myeloid LeukemiaPhase 2NCT05955261
A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia
A Phase 2 study testing Venetoclax, Azacitidine and Cytarabine in people with Acute Myeloid Leukemia, run by St. Jude Children's Research Hospital at 10 sites in United States.
Trial summary
This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients with newly diagnosed acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 29 days to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Venetoclax, Azacitidine and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 10 sitesUnited States
- Study dates
- 25 Jul 2023to Mar 2034
- Phase
- Phase 2
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 29 days to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of AML fulfilling the criteria of the WHO classification of myeloid neoplasms or < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality or myeloid sarcoma or primary myelodysplastic syndrome (MDS) with ≥ 10% blasts or a complete blood count with the presence of at least 1,000 blasts/μL (e.g., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count ≥ 5,000/μL with ≥ 20% blasts
- Age > 28 days and < 22 years
- No prior therapy for this malignancy except for one dose of intrathecal therapy and hydroxyurea or low-dose cytarabine (≤ 200 mg/m^2 per day for ≤ 7 days)
- Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment
- Male and female participants of reproductive potential must agree to use an effective contraceptive method during the study and for 6 months after study treatment
- Written informed consent from the patient and/or parent/legal guardian
- Direct bilirubin ≤ 1.5 x institutional upper limit of normal
Who cannot join
- Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
- Uncontrolled systemic fungal, bacterial, or viral infection or significant concurrent disease that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results
- Prior exposure to any dose of anthracycline or anthracenedione
- Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of enrollment
- Patients may not receive moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) within 3 days of enrollment.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 1 recruiting
- Suspended
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
- Suspended
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
- Active, not recruiting
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
- Suspended
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
- Suspended
Cook Children's Medical Center
Fort Worth, Texas, 76104
- Suspended
Valley Children's Hospital
Madera, California, 93636
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Hiroto Inaba, MD, PhD, 888-226-4343, referralinfo@stjude.org
Hiroto Inaba, MD, PhD
- Suspended
Children's Hospital of Orange County
Orange, California, 92868
- Suspended
Rady Children's Hospital-San Diego
San Diego, California, 92123
- Suspended
Children's National Medical Center
Washington D.C., District of Columbia, 20020
About this study
Official title: A Collaboration Phase 2 Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia
This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients with newly diagnosed acute myeloid leukemia (AML).
Primary Objectives:
- Establish the tolerability adding venetoclax to standard chemotherapy in pediatric patients with AML
- Estimate the proportion of patients who become minimal residual disease (MRD) negative by flow cytometry after one course of venetoclax-based induction therapy
Secondary Objectives:
- Estimate the rates of complete remission (CR), event-free survival (EFS), and overall survival (OS) in pediatric patients who receive venetoclax-based chemotherapy
Read the detailed description
Treatment will be based on genetic characteristics and response to therapy. Venetoclax will be given with each course of therapy. Low-risk patients will receive four courses of chemotherapy and intermediate-risk patients will receive five courses. High-risk patients who do not have a suitable stem cell donor or who decline HCT will receive five courses of chemotherapy. The definition of suitable stem cell donor and the conditioning regimens used for HCT will be determined by local institutional protocols or guidelines.
Intervention:
Low Risk
Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.
Induction 2: Venetoclax PO QD on days 1-14, cytarabine IV over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, and etoposide IV over 1 hour QD on days 1-5.
Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1 and then venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28 during intensification 1 and 2.
Intermediate Risk
Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.
Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.
Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1, venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2, and then venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5 during intensification 3. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28 during intensification 1-3.
High Risk
Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.
Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.
Intensification: Patients with MRD < 0.1% proceed directly to HCT if donor is available. If a donor is not yet available, patients with MRD < 0.1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD 0.1% to < 1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD >= 1% may receive venetoclax PO QD on days 1-10, azacitidine IV over 30 minutes QD on days 1-5, and high-dose cytarabine IV over 3 hours every 12 hours on days 6, 8, and 10. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Venetoclax, Azacitidine, Cytarabine, Gemtuzumab Ozogamicin, Daunorubicin Hydrochloride
- 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
Also called Venclextra, ABT-99
Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.
AzacitidineDrug
Also called Mylosar, Vidaza
Given IV over 30 minutes on days 1-5
CytarabineDrug
Also called Ara-C, Cytosar-U®
Given IV over 30 minutes q12 hours on days 1-8 (16 doses)
Gemtuzumab OzogamicinDrug
Also called Mylotarg
Given IV
Daunorubicin HydrochlorideDrug
Also called FI-6339, L-lyxo-Hexopyranoside
IV over 1 hour on days 1, 3, and 5
Also called SH T 586
Given IV over 30 minutes on days 1-5
Idarubicin HydrochlorideDrug
Also called IMI-30, Zavedos
Given IV over 15 minutes on days 3-5
Mitoxantrone HydrochlorideDrug
Also called Neotalem, Pralifan, Novantrone
IV over 1 hour on days 2-4
EtoposideDrug
Also called VP-16, Vepesid®
Given IV over 1 hour on days 1-5
GilteritinibDrug
Also called Xospata
PO on days 8-28 (21 doses)
| Study group | Role | What they receive |
|---|---|---|
| Low Risk | Experimental | All eligible patients receive intervention according to the Detailed Description section with the following:
Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Gemtuzumab Ozogamicin, Etoposide, Mitoxantrone Hydrochloride, Gilteritinib Receives: Drug: Venetoclax; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Idarubicin Hydrochloride; Drug: Mitoxantrone Hydrochloride; Drug: Etoposide; Drug: Gilteritinib |
| Intermediate Risk | Experimental | All eligible patients receive intervention according to the Detailed Description section with the following:
Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Mitoxantrone Hydrochloride, Gilteritinib Receives: Drug: Venetoclax; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Fludarabine Phosphate; Drug: Idarubicin Hydrochloride; Drug: Mitoxantrone Hydrochloride; Drug: Etoposide; Drug: Gilteritinib |
| High Risk | Experimental | All eligible patients receive intervention according to the Detailed Description section with the following:
Venetoclax, Azacitidine, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Gilteritinib Receives: Drug: Venetoclax; Drug: Azacitidine; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Fludarabine Phosphate; Drug: Idarubicin Hydrochloride; Drug: Etoposide; Drug: Gilteritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal residual disease (MRD)-negativity rate
Will compute a binomial confidence interval for the proportion of MRD-evaluable patients who become MRD-negative (defined as MRD < 0.1%) after induction 1.
Measured: At day 29 after induction 1
Incidence of death or unacceptable adverse event
A patient is deemed to have tolerated a course of therapy if they complete that course without death or an unacceptable adverse event. Will monitor the tolerability or each course using multi-stage binomial stopping rules. Will use the method of Jung and Kim to compute 95% confidence intervals that adjust for the multi-stage monitoring.
Measured: From initiation to completion of each course of therapy, an average of 6 weeks
Secondary outcomes (2)
Event-free survival
The Kaplan-Meier method will be used and 95% confidence intervals will be computed for event-free survival at 3 years.
Measured: From study enrollment to disease resistance, relapse, development of a second malignancy, or death due to any cause (up to 3 years after the last enrollment).
Overall survival
The Kaplan-Meier method will be used and 95% confidence intervals will be computed for overall survival at 3 years.
Measured: From protocol enrollment until death (up to 3 years after the last enrollment).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2023
- Study start25 Jul 2023
- Primary completionDec 2026 (estimated)
- Study completionMar 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Hiroto Inaba, MD, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05955261
- Sponsor's protocol ID
- AML23
- Other IDs
- NCI-2023-04138
- Status last verified
- Sep 2026
- First submitted
- 20 Jun 2023
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.