Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia

Phase 3

Active, not recruiting

• Conditions: Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia
• Interventions: Drug: Blinatumomab

• Registration Number: NCT05327894
• Lead Sponsor: Princess Maxima Center for Pediatric Oncology

Brief Summary

This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.

Detailed Description

All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as \< 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.

Study Timeline

• Study First Submitted: 2022-04-07
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-14
• Study Start: 2022-12-15
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-28
• Last Update Posted: 2025-07-31
• Primary Completion: 2027-09
• Study Completion: 2030-09-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) 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 parent(s) or other legally authorized guardian of the patient according to local law and regulations.

Exclusion criteria for blinatumomab:

1. KMT2A-wildtype patients.
2. Multilineage MPAL
3. T-ALL.
4. Age > 365 days at the time of diagnosis.
5. Down syndrome.
6. Relapsed ALL.
7. 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.

If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
High risk (HR)	Blinatumomab	Subject is defined as HR if \< 6 months of age with WBC \> 300 at diagnosis OR poor prednisone response. Also MR patients with end of induction MRD ≥ 1%, or MRD \> 0.01% after the 1st cycle of blinatumomab, will be allocated to HR treatment. Subject gets 1 cycle of blinatumomab. Thereafter patient is eligible for hematopoietic stem cell transplantation (HSCT) with or without experimental therapy in an investigational window.
Medium Risk (MR)	Blinatumomab	Subject is defined as MR if \> 6months of age at diagnosis, OR \< 6 months of age with White Blood cell Count (WBC) \< 300 at diagnosis and good prednisone response. Subject gets 1st cycle of blinatumomab. If MRD is \>0.01%, after 1st cycle of blinatumomab, subject will be allocated to HR treatment from that phase, and will be eligible for HSCT. If MRD is undetectable or \< 0.01% after the 1st cycle of blinatumomab (TP2) patient will be eligible for replacement of MARMA by 2nd cycle of blinatumomab after receipt of lymphoid style consolidation (Protocol IB) or of myeloid style consolidation (ADE/MAE).

Primary Outcome Measures

Name	Time	Method
Event free survival (EFS).	5 years	The primary endpoint is EFS, defined as the time from diagnosis to resistance to induction, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up (censored) for patients without events.

Secondary Outcome Measures

Name	Time	Method
Overall survival	8 years	The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy.
CD19 (cluster of differentiation antigen 19) negative relapse	8 years	Proportion of CD19 negative relapses in the entire study cohort and according to risk group
Myeloid lineage switches	8 years	Proportion of myeloid lineage switches in the entire study cohort and according to risk group
Endpoints by risk group	8 years	The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy.
Outcome for the entire study cohort and according to risk group	8 years	Outcome for the entire study cohort and according to risk group will be evaluated in terms of the protocol specific definition of EFS follows: the time from diagnosis to, resistance to proto-col, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up for patients without events. Cumulative incidence (or percentage) of resistance, CIR, death in CR and second malignancy will also be estimated.
Minimal Residual Disease	8 years	MRD response as defined in the protocol and frequencies of MRD levels
Grade ≥3 adverse event	8 years	Proportion of grade ≥3 adverse event (AEs) during the blinatumomab course(s). Proportion of adverse events of special interest (AESIs) and serious adverse events (SAEs) in all protocol phases.
Grade ≥2 cardiac disorders	5 years	Proportion of grade ≥2 cardiac disorders at 2 and 5 years after diagnosis
Overall survival after 1st relapse	8 years	Overall survival (OS) after first relapse, defined as the time from first relapse to death from any cause, in the entire study cohort and according to risk group

Trial Locations

Locations (90)

Hospital de Pediatría S.A.M.I.C. "Juan P. Garrahan"; 🇦🇷 Buenos Aires, Argentina

Australian and New Zealand Children's Haematology/Oncology Group; 🇦🇺 Clayton, Victoria, Australia

North Adelaide- Womens and Childrens Hospital; 🇦🇺 Adelaide, Australia

Monash Children's Hosptial; 🇦🇺 Clayton, Australia

New Lambton Heights- John Hunter Children's Hospital; 🇦🇺 New Lambton Heights, Australia

Royal Children's Hospital (Children's Cancer Centre); 🇦🇺 Parkville, Australia

Perth Children's Hospital; 🇦🇺 Perth, Australia

Queensland Children's Hospital; 🇦🇺 South Brisbane, Australia

Sydney Childrens Hospital; 🇦🇺 Sydney, Australia

The Childrens Hospital at Westmead; 🇦🇺 Westmead, Australia

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