Phase 2 Clinical Trial for Newly Diagnosed Pediatric Acute Promyelocytic Leukemia: AML-P17

JRCT ID: jRCTs031230727

Registered date:21/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Newly Diagnosed Pediatric Acute Promyelocytic Leukemia
• Date of first enrollment: 21/03/2024
• Target sample size: 39
• Study type: Interventional
• Intervention(s): The introduction of differentiation induction therapy using ATRA and ATO for newly diagnosed pediatric APL in Japan has completely obviated the need for intravenous chemotherapy for SR-APL (WBC <10,000/microL at diagnosis) and intravenous chemotherapy for HR-APL (other than SR). We intend to conduct a multicentric, prospective phase II clinical trial (AML-P17) aimed at evaluating the feasibility of reducing chemotherapy drug use, improving the cure rate, and verifying the safety and effectiveness of ATRA + ATO skeletal treatment. The trial will be designed as a single-group trial per risk group with a 5-year enrollment period, 2-year observation period, and a target number of 39 patients. The study treatment for SR-APL will be induction therapy consisting of ATRA 25 mg/m2/day and ATO 0.15 mg/kg/day administered for up to 60 days until hematological remission is achieved. For HR-APL, idarubicin 12 mg/m2/day will be administered up to two times as induction therapy for SR-APL. Maintenance therapy will be given for SR-APL and HR-APL and will consist of seven courses of ATRA at the same dosage as in the induction therapy for 2 weeks followed by 2 weeks off. The same dosage regimen will be used for ATO, with 4 weeks (20 days) on and 4 weeks off. Four courses of the regimen will be administered in total.

Outcome(s)

• Primary Outcome: Two-year event-free survival

Secondary Outcome

(1) Two-year molecular event-free survival (mEFS)
(2) Remission induction rate
(3) Molecular biological complete response rate at the end of treatment
(4) Two-year overall survival (OS)
(5) Cumulative incidence rate (CIR)
(6) Non-relapse mortality (NRM)
(7) Incidence rate of CTCAE ver. 5.0 grade 3 or higher APL-DS, DIC
(8) EFS, OS, CIR, NRM, remission induction rate, and molecular biological complete remission rate by age group and risk group
(9) EFS, OS, CIR, and NRM for BMA-2, BMA-3, and MRD
(10) EFS, OS, CIR, NRM, remission induction achievement rate, and molecular biological complete remission rate by induction therapy duration
(11) Quality of life (QOL) assessment of the patient using a questionnaire survey administered to the patient or the family (proxy evaluation)

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 19age old
• Gender: Both

Include criteria

(1) Presence of acute promyelocytic leukemia (FAB-M3) according to the FAB classification in a patient aged < 19 years at diagnosis.
APL is diagnosable and AML-P17 registration is possible if the morphological characteristics of FAB classification M3 are met. The percentage of blasts in the bone marrow at the time of diagnosis may be less than 20%.
(2) A test for PML::RARA gene rearrangement must be done using PCR or FISH.
(3) Untreated new patients or patients who have begun treatment with ATRA and/or DEX for APL-DS within 3 days. However, steroid administration and a single intrathecal administration of methotrexate are both permitted if ALL is suspected.
(4) Performance or scheduling of one of the following tests at the time of the initial consultation: chromosome testing, FISH, PCR
If the specimen cannot be submitted due to a holiday, etc., it should be submitted at the earliest opportunity (a peripheral blood sample is also acceptable). In the latter case, a sample obtained after the start of ATRA may be used.
(5) The ECOG performance status (PS) score or the JPLSG Infantile Leukemia Committee PS score of 0 to 3. However, a PS score of 4 is still eligible if the cancer is thought to be AML.
(6) Patients with sufficient organ function who meet the following two conditions based on test values obtained within 7 days of case registration:*
T-Bil value< 3 times the upper limit of the age-specific test standard value.
Creatinine value< 3 times the upper limit of the age-specific test standard value.
*Cases in which the abnormality is thought to be caused by leukemia and improves with leukemia treatment. Patients may be eligible if there is a high probability that they will fulfill both criteria.
(7) Written consent for trial participation obtained from the applicant or his/her legal guardian.

Exclude criteria

(1) Patients with secondary APL after anticancer drug therapy or radiation therapy.
(2) t(15;17)(q22;q12)-negativity and PML::RARA fusion gene negativity (the test results must be confirmed at the registration stage).
(3) Presence of an uncontrolled infection, including active tuberculosis, HBV infection, HCV infection, and HIV antibody-positivity.
(4) Patients who are pregnant; may become pregnant; or are breastfeeding.
(5) A history of hematopoietic stem cell transplantation or organ transplantation.
(6) A history of congenital or acquired immunodeficiency syndrome.
(7) Presence of an organ disorder interfering with study treatment.
a) Presence of uncontrolled heart failure (heart disease alone is not excluded)
b) Presence of uncontrolled renal failure
c) Presence of respiratory failure requiring ventilator management
d) Presence of CTCAE ver 5.0 grade 3 or higher intracranial hemorrhage
(8) QTfc prolongation (450 msec or more) or a personal or family history of long QT syndrome
(9) Other reasons deemed unsuitable for participation by the attending physician.

Related Information

• Primary Sponsor: Yuza Yuki
• Source(s) of Monetary Support: Tokyo Metropolitan Hospital Organization,Japan Leukemia Research Fund