Trial Title:
A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia
NCT ID:
NCT05955261
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Fludarabine
Fludarabine phosphate
Etoposide
Azacitidine
Venetoclax
Daunorubicin
Mitoxantrone
Idarubicin
Gemtuzumab
Gilteritinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
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.
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
Venclextra
Other name:
ABT-99
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Given IV over 30 minutes on days 1-5
Arm group label:
High Risk
Other name:
Mylosar
Other name:
Vidaza
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IV over 30 minutes q12 hours on days 1-8 (16 doses)
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
Ara-C
Other name:
Cytosar-U®
Intervention type:
Drug
Intervention name:
Gemtuzumab Ozogamicin
Description:
Given IV
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
Mylotarg
Intervention type:
Drug
Intervention name:
Daunorubicin Hydrochloride
Description:
IV over 1 hour on days 1, 3, and 5
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
FI-6339
Other name:
L-lyxo-Hexopyranoside
Intervention type:
Drug
Intervention name:
Fludarabine Phosphate
Description:
Given IV over 30 minutes on days 1-5
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Other name:
SH T 586
Intervention type:
Drug
Intervention name:
Idarubicin Hydrochloride
Description:
Given IV over 15 minutes on days 3-5
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
IMI-30
Other name:
Zavedos
Intervention type:
Drug
Intervention name:
Mitoxantrone Hydrochloride
Description:
IV over 1 hour on days 2-4
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
Neotalem
Other name:
Pralifan
Other name:
Novantrone
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given IV over 1 hour on days 1-5
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
VP-16
Other name:
Vepesid®
Intervention type:
Drug
Intervention name:
Gilteritinib
Description:
PO on days 8-28 (21 doses)
Arm group label:
High Risk
Arm group label:
Intermediate Risk
Arm group label:
Low Risk
Other name:
Xospata
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).
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
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 sorafenib 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 sorafenib 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
sorafenib 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 sorafenib 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 sorafenib PO
QD on days 8-28.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Gender:
All
Minimum age:
29 Days
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Valley Children's Hospital
Address:
City:
Madera
Zip:
93636
Country:
United States
Status:
Recruiting
Contact:
Last name:
Faisal Razzaqi, MD
Phone:
559-353-3000
Email:
frazzaqi@valleychildrens.org
Investigator:
Last name:
Faisal Razzaqi, MD
Email:
Principal Investigator
Facility:
Name:
St. Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hiroto Inaba, MD, PhD
Phone:
866-278-5833
Email:
referralinfo@stjude.org
Investigator:
Last name:
Hiroto Inaba, MD, PhD
Email:
Principal Investigator
Start date:
July 25, 2023
Completion date:
March 2034
Lead sponsor:
Agency:
St. Jude Children's Research Hospital
Agency class:
Other
Collaborator:
Agency:
AbbVie
Agency class:
Industry
Source:
St. Jude Children's Research Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05955261
http://www.stjude.org
http://www.stjude.org/protocols
