A phase III randomized trial for B-cell precursor ALL

JRCT ID: jRCTs041210040

Registered date:13/07/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: B cell precursor Acute Lymphoblastic Leukemia
• Date of first enrollment: 13/07/2021
• Target sample size: 2000
• Study type: Interventional

Intervention(s)

The patients are divided into 4 groups based on risk classification and treated in each group as follows. Risk classification is performed based on age, white blood cell count at diagnosis, leukemic biology, and treatment response including prednisone-response and minimal residual disease kinetics.
-Low risk (LR)
The patients in the LR group are randomly assigned to receive either reduced-intensity treatment based on JACLS ALL-02 SR backbone or standard treatment based on B12 SR.
-High risk (HR)
The patients in the HR-non stem cell transplantation (SCT) group are randomly assigned to receive either standard BFM backbone treatment (6 blocks) or experimental treatment (3 blocks and 2 cycles of blinatumomab).
-LR/Standard risk (SR)/ Intermediate risk (IR) /HR-non SCT
The patients in all groups except HR-SCT are randomly assigned to receive either short-term maintenance treatment (18 months), standard maintenance treatment (24 months), or long-term maintenance treatment (30 months) based on their sex and leukemic biology.

Outcome(s)

Primary Outcome

Five years event free survival in RCT-LR
Five years event free survival in RCT-HR
Five years event free survival in RCT-S
Five years event free survival in RCT-L

Secondary Outcome

(1) Five years event free survival/overall survival of the whole group
(2) Five years event free survival/overall survival of each risk group
(3) Five years event free survival/overall survival of age and cumulative incidence of relapse (CI-R)/cumulative incidence of non-relapse mortality (CI-NRM)
(4) Five years overall survival in RCT-S and RCT-L, and cumulative incidence of relapse (CI-R)/ cumulative incidence of non-relapse mortality(CI-NRM)
(5) Five years overall survival in RCT-LR and RCT-HR, and cumulative incidence of relapse (CI-R)/cumulative incidence of non-relapse mortality(CI-NRM)
(6) Remission rate after induction chemotherapy and MRD negative rate
(7) Incidence of adverse events
(8) Incidence of deep mycosis by treatment phase
(9) Incidence of deep mycosis with or without prophylactic antifungal drugs
(10) Completion rate of study
(11) Five years event free survival rate and 6-MP dose per NUDT15 gene polymorphism
(12) Late complications
(13) Search for prognostic factors involved in the outcome
(14) Estimation of quality of life (QOL) by Questionnaire survey to patients and families
(15) Replacement rate to Erw-ASP.Five years overall survival in ASP replacement group, non-replacement group, discontinuation group, and cumulative incidence of relapse (CI-R)

Key inclusion & exclusion criteria

• Age minimum: >= 1age old
• Age maximum: < 65age old
• Gender: Both

Include criteria

(1) Diagnosis of B cell precursor ALL or pre-B-ALL
(2) Consent to FCM and fusion-gene screening
(3) Age >=1 year and < 65 years old at diagnosis
(4) ECOG performance status (PS) score of 0-2. However, PS scores up to 3 are permitted when the deterioration of PS is thought to be due to leukemia.
(5) Sufficient organ function satisfying the laboratory data listed below;
-Direct bilirubin <=2.0 mg/dL or within 3x of age-adjusted upper-limit of normal range if the patient is under 16-year-old
-Creatinine <=2.0 mg/dL or within 3x of age-adjusted upper-limit of normal range if the patient is under 16-year-old
-Normal ECG and UCG
-SpO2 >= 94% in room air
(6) Written informed consent obtained from patient or guardians.

Exclude criteria

(1)BCR-ABL1 positive ALL
(2)Down syndrome
(3)Malignant hypertension
(4)Pulmonary fibrosis
(5)Interstitial pneumonia
(6)Liver cirrhosis
(7)Positive anti-HIV antibody or HBs antigen
(8)Uncontrolled diabetes
(9)Uncontrolled infection
(10)Deep thrombosis requiring treatment.
(11)Mental disorder that will likely make it impossible to complete treatment according to the protocol
(12)Active double cancer
(13)Pregnant or lactating woman, or high possibility of pregnancy
(14)Past History of congenital or acquired immunodeficiency
(15)Any inappropriate status judged by the physician

Related Information

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