Trial Title:
Molecular Subtype Combined with Early Minimal Residual Disease to Optimize the Treatment of Newly Diagnosed Acute Myeloid Leukemia
NCT ID:
NCT06652685
Condition:
Acute Myeloid Leukemia (AML)
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm, Residual
Venetoclax
Conditions: Keywords:
Acute myeloid leukemia
venetoclax
gilteritinib
D5-PBCR
Risk-stratified
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Subjects receive IA regimen as the initial induction. On day five of induction, D5-PBCR
will be tested according to protocol. Patients will be assigned to different arms
according to the result of D5-PBCR.
For FLT3 mutate patients, a combination of gilteritinib will be recommended in this
study. Induction and consolidation phase: gilteritinib 80mg on D8-14.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
D5-PBCR(-) IA arm
Description:
Induction: IA Drug: idarubicin, intravenously, 10 mg/m^2 on D1-3 Drug: cytarabine,
intravenously, 100 mg/m^2 on D1-7
Consolidation:
Subjects who achieve composite complete remission (CRc) proceed with consolidation
therapy.
In consolidation therapy phase, subjects in the group with favorable/intermediate risk
and MRD negetive, will receive cytarabine intravenously at 2g/m^2/q12h*6 doses. Subjects
in the group with adverse risk or MRD positive will receive cytarabine intravenously at
2g/m^2/q12h*6 doses together with venetoclax 400mg on D4-10. Dose ramp-up of venetoclax
is not required.
After two cycles of consolidation, a multi-disciplinary team will discuss whether the
patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN
risk stratification and MRD status.
Arm group label:
D5-PBCR(-)
Intervention type:
Drug
Intervention name:
D5-PBCR(+) IA+Venetoclax arm
Description:
Induction: IA+Ven Drug: idarubicin, intravenously, 10 mg/m^2, on D1-3, Drug: cytarabine,
intravenously, 100 mg/m^2 on D1-7 For D5-PBCR (+) patients, Venetoclax will be combined.
Drug: Venetoclax. Orally once daily, on D6-14. A 3-day dose ramp-up is required for the
first induction (100mg D6, 200mg D7, 400mg D8-14) If a second induction is needed, the
dose of IA is the same as the first cycle, and dose ramp-up of venetoclax is not
required.
Consolidation:
Subjects who achieve composite complete remission (CRc) proceed with consolidation
therapy.
In consolidation therapy phase, subjects in the group will receive cytarabine
intravenously at 2g/m^2/q12h*6 doses together with venetoclax 400mg on D4-10. Dose
ramp-up of venetoclax is not required.
After two cycles of consolidation, a multi-disciplinary team will discuss whether the
patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN
risk stratification and MRD status.
Arm group label:
D5-PBCR(+)
Summary:
This study aims to investigate the safety and efficacy of drug "X" in combination with
intensive chemotherapy in subjects with newly diagnosed AML (excluding APL and CBF-AML).
"X" drugs included BCL-2 inhibitor venetoclax and FLT3 inhibitor Gilteritinib.
Subjects will receive standard intensive chemotherapy during induction and consolidation.
Early induction response will be evaluated according to the results of peripheral blood
blast clearance rate on the fifth day after induction therapy (D5-PBCR). Venetoclax will
be added in D5-PBCR positive subjects. For subjects with FLT3 mutations, Gilteritinib
will be combined.
Subjects will be stratified based on the genetic risk classification of 2022 European
LeukemiaNet recommendations (ELN risk) and MRD status to receive specific consolidation
therapy after the induction therapy.
Detailed description:
Young patients with naïve AML (excluding APL and CBF-AML) were included in this study.
218 subjects who meet the eligibility criteria will receive the standard 3+7 intensive
chemotherapy induction, containing cytarabine and idarubicin. On the basis of the IA
induction regimen, the early chemotherapy response was evaluated according to the results
of peripheral blood blast clearance rate on the fifth day after induction therapy
(D5-PBCR). For D5-PBCR-positive patients, venetoclax will be added to conventional
chemotherapy. For patients with FLT3 mutations, gilteritinib will be combined.
Subjects who achieve a composite complete remission (CRc) after induction therapy will
receive further consolidation therapy, which regimen will be decided based on the ELN
risk at diagnosis and MRD status detected by MFC and gene quantification after induction
therapy.
The purpose of the study is to determine whether the addition of drug "X" to the standard
induction regimen improves efficacy in the treatment of naïve AML.
Primary objective: To evaluate whether intensive IA combined with targeted drug (drug
"X") regimens can improve the composite response rate (CRc) after 1 course of induction
therapy in newly diagnosed young AML patients Secondary Objective: To evaluate whether
intensive chemotherapy combined with drug "X" during induction and consolidation can
improve overall response rates, overall survival, and event-free survival in newly
diagnosed young AML patients Safety indicators: incidence of adverse reactions during
treatment, recovery time of neutrophils and platelets
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Bone marrow morphology and immunology confirmed newly diagnosed AML patients
(according to 2022 ICC criteria)
2. Exclude patients with APL and CBF-AML (according to fusion genes and chromosomes)
3. Performance status score 0-2 (ECOG score)
4. Age 18~59 years old
5. Liver and kidney function: blood bilirubin ≤ 35 μmol/L, AST/ALT below 2 times the
upper limit of normal, creatinine ≤ 150 μmol/L
6. Normal cardiac function (EF ≥50%)
7. Obtained informed consent signed by the patient or family member
Exclusion Criteria:
1. FAB classification is M3, or confirmed APL at the molecular level
2. CBF-AML
3. Patients who have already been treated
4. Comfirmed central nervous system leukemia
5. Allergy to any of the drugs involved in the protocol
6. Medical condition or organ system dysfunction that precludes the inability to
swallow capsules or tablets, or has a disease that significantly affects
gastrointestinal function and/or inhibits small bowel absorption (including
malabsorption syndrome, small bowel resection, or poorly controlled inflammatory
bowel disease)
7. Cardiac function and disease consistent with one of the following: a) long QTc
syndrome or QTc interval >480 ms; b) second- or third-degree atrioventricular block;
Severe, uncontrolled cardiac arrhythmias requiring medication; c) United States New
York College of Cardiology Grade ≥ III; d) Ventricular ejection fraction (LVEF) less
than 50%; e) History of myocardial infarction, unstable angina, severe unstable
ventricular arrhythmia or any other arrhythmia requiring treatment, history of
clinically severe pericardial disease, or ECG evidence of acute ischemic or active
conduction abnormalities within 6 months prior to recruitment
8. Previous or present concomitant malignancies (except for basal cell carcinoma of the
skin that have been effectively controlled as non-melanoma, carcinoma in situ of the
breast/cervix, and other malignancies that have not been effectively controlled for
more than 6 months, and patients who have been receiving long-term non-chemotherapy
treatments such as hormonal therapy)
9. Significant abnormalities in liver and kidney function (serum bilirubin, aspartate
aminotransferase, alanine aminotransferase or serum creatinine more than 2 times the
upper limit of normal reference values; Excluded from AML-related as judged by the
investigator)
10. Patients who have previously used other drugs for the treatment of AML (except
hydroxyurea and cytarabine for cell count control), including but not limited to
BCL2, FLT3, IDH1, IDH2 inhibitors, or other drugs in clinical trials
11. Coagulopathy not associated with AML
12. HIV infection, syphilis infection, HCV infection, active HBV infection (HBsAg
positive, or HBsAg negative but HBcAb positive with HBV DNA > 1.0 ×ULN)
13. Other uncontrolled active infection (as judged by the investigator)
14. Pregnant or lactating women
15. Inability to understand or follow the study protocol
16. Participation in other relevant clinical studies within 30 days (except diagnostic
clinical studies)
17. Patients who in the opinion of the investigator, are not suitable to participate in
this study
Gender:
All
Minimum age:
18 Years
Maximum age:
59 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Address:
City:
Shanghai
Country:
China
Contact:
Last name:
Yang Shen
Phone:
+86-021-64370045
Email:
sy_clinicaltrial@163.com
Start date:
October 30, 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Ruijin Hospital
Agency class:
Other
Source:
Ruijin Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06652685
