An open-label randomized comparative trial of blinatumomab for B-cell acute lymphoblastic leukemia

JRCT ID: jRCT2031230581

Registered date:22/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: B-precursor ALL
• Date of first enrollment: 01/02/2024
• Target sample size: 180
• Study type: Interventional

Intervention(s)

- Control Arm: active comparator, other
Participants will receive MTX 20 mg/m^2 orally once weekly from weeks 1 through 74.
6-MP 50 mg/m^2 will be administered orally daily from weeks 1 through 74.
For subjects with NUDT15 homozygous variants, starting dose of 6-MP is reduced to 10 mg/m^2. Oral 6-MP and MTX should be adjusted depending on blood cell counts.
The amount of IT-MTX will be appropriate for the age at the start of maintenance therapy will be administered intrathecally on day 1 (4 times in total) of weeks 1, 9, 17, and 25.
Age at the start of maintenance
<1 year old; 6mg
1 year old; 8mg
2 years old; 10mg
>=3 years old ;12mg

- BLIN Arm: experimental, active comparator, other
Participants will receive intravenous blinatumomab continuously from week 1 to week 4 (28 days). Injections are followed by a 35-day treatment-free interval. And then receive intravenous blinatumomab continuously from week 10 to week 13 (28 days). See below for doses by patient weight.
>= 45kg :
28mcg
<45kg:
15mcg/m^2
MTX 20 mg/m^2 orally once daily per week from weeks 5 to 8 and from week 14 to 74.
6-MP 50 mg/m^2 will be administered orally daily from weeks 5 to 8 and from week 14 to 74.
For subjects with NUDT15 homozygous variants, starting dose of 6-MP is reduced to 10 mg/m^2. Oral 6-MP and MTX should be adjusted depending on blood cell counts.
The amount of IT-MTX will be appropriate for the age at the start of maintenance therapy will be administered intrathecally on day 1 (4 times in total) of weeks 1, 9, 17, and 25.
Age at the start of maintenance
<1 year old; 6mg
1 year old; 8mg
2 years old; 10mg
>=3 years old ;12mg

Outcome(s)

• Primary Outcome: Event-free survival (EFS)

Secondary Outcome

- Overall survival (OS)
- Time to relapse
- Time to non-relapse mortality
- Adverse event of CTCAE grade 4 or worse

Key inclusion & exclusion criteria

• Age minimum: >= 4weeks old
• Age maximum: <= 24age old
• Gender: Both

Include criteria

1. Participant must be 28 days to 24 years of age inclusive, at the time of signing the informed consent.
2. Participants who are diagnosed B-precursor ALL.
3. The risk stratification is IR.
4. Patients in complete remission after consolidation therapy.
5. The intention to use contraception during the 28-day period after the end of the administration of the investigational drug.
6. Provide written informed consent.

Exclude criteria

1. Pregnant or breastfeeding women, or suspected of being pregnant
2. A prior history of CD19-targeted therapy
3. Concurrent participating in a clinical trial
4. BCR-ABL1 positive
5. Having any of the following poor prognostic factors:
- MLL-AF4 positive or TCF3-HLF positive or hypodiploid (<=44 or DNA index <0.85)
- Non-CR on induction therapy
- PCR-MRD >=10^-3 at the end of early intensive therapy
- Central Nervous System (CNS) Infiltration at diagnosis (CNS3)
6. Mature B-cell lymphoblastic leukaemia
7. MYC gene translocation positive
8. Down Syndrome
9. Malignant hypertension
10. Pulmonary fibrosis
11. Interstitial pneumonia
12. Liver cirrhosis
13. Known infection with HIV or hepatitis B virus (HBsAg positive)
14. Poorly controlled diabetes mellitus
15. Uncontrolled infection
16. Deep thrombosis requiring treatment.
17. Psychiatric disorders that may prevent treatment according to the protocol
18. Active malignancy other than ALL
19. Past History of primary or acquired immunodeficiency
20. Any inappropriate status to participate in this clinical trial judged by the physician

Related Information

• Primary Sponsor: Kato Motohiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED), Amgen Inc.