A clinical trial of risk-stratification and gemtuzumab ozogamicin combined post-induction chemotherapy for children with AML

JRCT ID: jRCTs041210015

Registered date:10/05/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Acute Myeloid Leukemia
• Date of first enrollment: 11/05/2021
• Target sample size: 500
• Study type: Interventional

Intervention(s)

<Induction>
All registered patients will recieve two common induction chemotherapies.
Induction-1A (ECM): standard dose Ara-C, mitoxantrone (MIT), etoposide (VP-16), and triple intrathecal therapy [TIT; Ara-C, methotrexate (MTX), and hydrocortisone (HDC)].
Induction-2A (HCEI): high-dose Ara-C, idarubicin (IDA), VP-16, and TIT.

<Risk-stratification>
All patients who achieved hematological CR will be allocated to one of the three rsik groups according to the cytogenetic abnormalities and induction treatment response [both hematological response and minimal residual disease (MRD)].
Low-risk (LR) group: CBF-AML with both MRD<0.1% after Induction-1 and negative FLT3-ITD
Intermediate-risk (IR) group: CBF-AML with either MRD>=0.1% after Induction-1 or FLT3-ITD; non-CBF-AML without high-risk cytogenetics and MRD<0.1% after Induciton-1
High-risk (HR) group: Non-CBF-AML without high-risk cytogenetics and MRD>=0.1% after Induciton-1; AML with high-risk cytogenetics; non-CR after Induction-1

<Post-induction therapy>
(1) LR
Patients will receive Consolidation-1(HCM; high-dose Ara-C, MIT, TIT), Consolidation-2(HCI; high-dose Ara-C, IDA, TIT), and Consolidation-3(HC; high-dose Ara-C, TIT)
(2) IR and HR
Patients will be randomized to recieve either the experimental arm or the standard arm therapy. HR patients will receive allogeneic hematopoietic stem cell transplantation in first CR regardless of the randomized treatment arms.
a) Experimental arm: Consolidation-1[(HCM; high-dose Ara-C, MIT, TIT)+gemtuzumab ozogamicin (GO)], Consolidation-2(HCEI+GO), and Consolidation-3(HCM+GO)
b) Standard arm: Consolidation-1(HCM), Consolidation-2(HCEI), and Consolidation-3(HCM)

Outcome(s)

• Primary Outcome: 3-year disease-free survival (DFS) rate of the non-LR patients (IR and HR)

Secondary Outcome

CR rate
Overall survival (OS)
Event-free survival (EFS)
Cumulative incidence of relapse (CIR)
Non-relapse mortality (NRM)
Incidence of grade 3 or higher aderse events defined by CTCAE ver.5.0
Evaluation of the patients' Quality of Life (QOL) obtained from the patients' family questionnaire
OS, EFS, CIR, and NRM according to the MRD levels at TP1
Rate of transplant-related complications and mortality at day 100 and at one year
Incidence of invasive fungal infections according to the GO randomization
Incidence of invasive fungal infections according to the use of prophylactic anti-fungal agents
Incidence of bacterial infections according to the use of prophylactic antibiotics

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 16age old
• Gender: Both

Include criteria

(1) Diagnosis of AML
(2) Age 0 to <16 years at diagnosis
(3) ECOG performance status (PS) score or JPLSG Infant Leukemia Committee PS score of 0 to 3; those with PS score 4 is also eligible if that is derived from AML
(4) Newly diagnosed AML without prior therapy for AML; history of steroid, ATRA due to suspicion of APL, or single intrathecal methotrexate due to suspicion of ALL are permitted
(5) Sufficient organ function meeting both laboratory data listed below (should be evaluated =<7 days of trial entry);
Serum T-Bil: <3x of the age-dependent normal range
Serum creatinine: <3x of the age-dependent normal range
(6) Prior consent to participating the JPLSG-CHM-14 study is mandatory
(7) Written informed consent from the legal guardian.

Exclude criteria

(1) <36 week and 0 day gestational age, if age =<30 days at diagnosis
(2) Patients with following diagnosis
1) RARA-associated fusion gene positive acute promyelocytic leukemia (APL)
2) AML associated with Down Syndrome (ML-DS)
3) Secondary AML (history of congenital bone marrow failure syndrome, myelodysplastic syndrome, and/or prior chemotherapy)
4) Ambiguous lineage acute leukemia (ALAL). ALAL with AML-specific genetic abnormalities are eligible
5) Myeloid sarcoma
(3) Uncontrollable infections (including active tuberclosis, HBV, and/or HCV)
(4) Pregnant or lactating females
(5) History of congenital or acquired immunodeficiencies
(6) Presence of organ dysfunction interfering trial therapy
a) Uncontrollable heart failure (presence of heart anomly itself is not a exclusion criteria)
b) Uncontrollable renal failure
c) Respiratory failure requiring mechanical ventilation
d) >= grade 3 intracranial hemorrhage (CTCAE ver 5.0)
(7) Presence of other malignant neoplasms
(8) Other inappropriate status judged by physician
(9) Patients considered as inappropriate to participate in the trial judged by the primary investigators and co-investigators

Related Information

• Primary Sponsor: Tomizawa Daisuke
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development