Multicenter, phase II study of arsenic trioxide and all-trans retinoic acid in patients with newly diagnosed acute promyelocytic leukemia in Japan (JALSG-APL220)

JRCT ID: jRCTs041200102

Registered date:15/02/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: acute promyelocytic leukemia
• Date of first enrollment: 18/02/2021
• Target sample size: 99
• Study type: Interventional

Intervention(s)

1. Induction therapy
All-trans retinoic acid (ATRA) + arsenic trioxide (ATO)
ATRA 45 mg/m2 is administered orally starting on day 1. ATRA is continued until hematological CR or for a maximum of 60 days.
ATO 0.15 mg/kg is administered intravenously starting on day 1. ATO is continued until hematological CR or for a maximum of 60 days;
For patients with initial white blood cell count > 10,000 /microL, ATO is started from day 5, and idarubicin 12 mg/m2 is added intravenously on days 1, 2.

2. Intrathecal chemotherapy
methotrexate 15 mg + cytarabine 40 mg + prednisolone 10 mg, before consolidation therapy.

3. Consolidation therapy
ATRA 45 mg/m2 is administered for 2 weeks on 2 weeks off, for a total of 7 cycles.
ATO 0.15 mg/kg is administered for 20 days in 4 weeks thereafter 4 weeks off, for a total of 4 cycles.

Outcome(s)

• Primary Outcome: 2-year EFS with stratification by the risk of APL

Secondary Outcome

Incidence of adverse events
Incedence of disseminated intravascular coagulation
Rate of complete remission
2-year and 3-year EFS, RFS, OS
3-year EFS with stratification by the risk of APL
2-year and 3-year RFS and OS with stratification by the risk of APL
2-year and 3-year EFS, RFS, OS with stratification by age
Comparison of 3-year EFS, RFS, OS between the present study and the historical controls (APL-97, -204, -212, -212G)

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Clinically diagnosed, untreated acute promyelocytic leukemia. PML-RARA must be positive or at least under testing by PCR at the time of registration.
2. Patients who have been informed that they have acute promyelocytic leukemia.
3. Age >= 16.
4. ECOG performance status 0 - 2.
5. Sufficient cardiac, pulmonary, hepatic, and renal functions to receive the treatment.
The criteria are as follows;
Total bilirubin < 2.0 mg/dL.
Serum creatinine < 2.0 mg/dL.
Cardiothoracic ratio <= 50% on a P-A chest X-ray. In case of cardiomegaly, LVEF >= 50% in echocardiography.
PaO2 >= 60 mmHg or SpO2 >= 93% in room air.
No severe abnormalities on electrocardiogram. QTc < 500 msec (using QTcF formula).
6. Written informed consent. For patients younger than 20 years, consent of the person in charge is also required.
7. Asian patients.

Exclude criteria

1. Extramedullary disease.
2. APL arising from myelodysplastic syndromes, or atypical leukemia.
3. Absence of PML-RARA rearrangement.
4. Uncontrollable infectious diseases including active tuberculosis.
5. Viral infections which require treatment with antivirus agents. Patients with COVID-19 or asymptomatic SARS-CoV-2 infection. Patients wiht herpes simplex which can be controlled by local treatment are not excluded.
6. Severe comorbidities such as malignant hypertension, congestive heart failure, renal failure, hepatic failure, acute myocardial infaction within 3 months before registration, severe arrhythmia, liver cirrosis, severe non-controlled diabetes, pulmonary fibrosis, interstitial pneumonia, active pneumonia under treatment, requirement of oxygen inhalation, gastrointestinal or respiratory tract hemorrhage, etc.
7. Human immunodificiency virus (HIV) infection. Active hepatitis B or C (Inactive carrier is allowed).
8. Other active malignancies.
9. Pregnant or breast-feeding women.
10. Severe psychiatric disease.
11. Patients with contraindications to ATRA or ATO
12. Patients who are considered by the investigator to be ineligible.

Related Information

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