Interfant-21

JRCT ID: jRCTs051230126

Registered date:10/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: acute lymphoblastic leukemia
• Date of first enrollment: 10/11/2023
• Target sample size: 16
• Countries of recruitment: Netherlands,Japan,Italy,Japan,Australia,Japan,New Zealand,Japan,Germany,Japan,Austria,Japan,Switzerland,Japan,the Czech Republic,Japan,Belgium,Japan,France,Japan,Nordic Countries,Japan,Ireland,Japan,Argentina,Japan,Hong Kong,Japan,Chile,Japan,Poland,Japan,Portugal,Japan,Israel,Japan,Hungary,Japan,Slovakia,Japan,Spain,Japan,Saudi Arabia,Japan
• Study type: Interventional

Intervention(s)

Phase 1 Induction
The first five weeks of your child's treatment are called Induction. In this phase a combination of drugs is given with the aim to destroy as many leukemia cells as possible. How intensive the next stages of treatment are depends on the response of the disease to the therapy (MRD).
Phase 2 Immunotherapy with blinatumomab
This phase is given to all children. The course of blinatumomab consists of a 4-week continuous infusion. Most of the times your child will be hospitalized for the first 4 days after the start of the infusion. After that, the treatment is on an outpatient basis, where the infusion of blinatumomab is changed twice a week in the hospital.
Phase 3 Consolidation 1 (Protocol IB or ADE/MAE)
After the induction course and the blinatumomab course, chemotherapy is given again to destroy the leukemia cells still present, which you can no longer see in blood or bone marrow. Which drugs exactly depend on the response of the disease to the first induction course. This treatment phase lasts approximately 6 to 8 weeks.
Phase 4 Consolidation 2 (2nd cycle of blinatumomab or MARMA)
Patients who have responded well to the 1st course of blinatumomab are eligible for a 2nd course of blinatumomab of 4 weeks. Patients who have responded less well to the 1st course of blinatumomab will receive the MARMA chemotherapy course. This MARMA course lasts 6 to 8 weeks, and consists of four hospitalizations of approximately 3 days. In addition, medication is also given at home.
Phase 5 Intensification (OCTADA(D)
This chemotherapy phase lasts about 9 weeks. The medication is given at the outpatient clinic/day treatment. In addition, medication is also given at home. Hospitalization is only necessary if your child has side effects such as fever.
Phase 6 Maintenance
This is the longest, but least intensive phase of the treatment. The goal of this phase is to reduce the risk of the leukemia coming back. This phase lasts until two years after the end of the Induction phase. The drugs can be taken at home. Furthermore, your child only needs to come to the outpatient clinic for check-ups. Your child only needs to be hospitalized if there are problems such as an infection.

Outcome(s)

• Primary Outcome: The primary objective is to improve the outcome (in terms of event-free survival (EFS) as the primary endpoint) of newly diagnosed KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) compared with the historical results of the Interfant-06 protocol.

Secondary Outcome

Secondary study objectives
1.To estimate overall survival (OS) and compare it with corresponding historical results of the Interfant-06 protocol, in the whole study and by risk group.
2.To determine outcome (in terms of secondary endpoint 2) according to risk group and compare it with corresponding historical results of the Interfant-06 protocol.
3.To determine outcome (in terms of secondary endpoint 3) taking into account the protocol-specific definition of resistance.
4.To assess the response to different treatment phases in term of minimal residual disease (MRD) response.
5.To evaluate the incidence of CD19 negative relapses
6.To evaluate the incidence of myeloid lineage switches
7.To describe the toxicity associated to each treatment phase
8.To describe long term cardiotoxicity
9.To evaluate survival after relapse, overall and by risk group.

Exploratory study objectives
1.Assessment of prognostic factors (e.g. age at diagnosis, white blood cell count at diagnosis (WBC), immunophenotype, type of KMT2A rearrangement, MRD, etc.)
2.To evaluate events after first relapse
3.To evaluate the concordance of MRD assessments by IG-TR PCR and KMT2A PCR, flow cytometry, and Next Generation Sequencing (NGS) (performed in some centers).
The objectives of the sub-studies are detailed in the sub-study protocols.

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: <= 12month old
• Gender: Both

Include criteria

1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement.
2. -<365 days of age at the time of diagnosis of ALL.
3. Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations.

Exclude criteria

1. KMT2A-germline patients.
2. T-ALL.
3. Age > 365 days at the time of diagnosis.
4. Relapsed ALL.
5. Treatment with systemic corticosteroids (equivalent prednisone >10 mg/m2/day) for more than one week and/or any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study.

Additional exclusion criteria for blinatumomab:
1. CD19 negative B-precursor ALL at diagnosis
2. CNS involvement (CNS2/CNS3 status) at the EOI. Patients with CNS disease at the time of diagnosis are eligible if CNS1 status is achieved prior to the start of the first blinatumomab cycle (lumbar puncture at ~day 33 of induction).
3. Proven hypersensitivity to the active substance or any of the excipients in blinatumomab.
4. Patients who have received a live vaccine 28 days prior to blinatumomab administration or plan to receive a live vaccine prior to B-cell recovery after the last dose of blinatumomab.
If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.

Related Information

• Primary Sponsor: Miyamura Takako
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,nonprofit organization deleteC Oomasari Research Grant,JCCG Omasari Research Grant