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

Acute Lymphoblastic Leukemia Clinical Trial

— Interfant-21  

Official title:

Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327894
• Other study ID #: 2021-000213-16
• Status: Recruiting
• Phase: Phase 3
• Start date: December 15, 2022
• Est. completion date: September 2030

Study information

• Verified date: April 2024
• Source: Princess Maxima Center for Pediatric Oncology
• Contact: Lieke van den Wildenberg
• Phone: 0031 88 972 72 72
• Email: trialmanagement[@]prinsesmaximacentrum.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: September 2030
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 365 Days

Eligibility

Inclusion Criteria:

1. Patients with newly diagnosed B- precursor acute lymphoblastic leukemia (ALL) or B- cell mixed phenotype acute leukemia (MPAL) according to the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017, with KMT2A-rearrangement.

2. =365 days of age at 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.

Exclusion 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 Conditions & MeSH terms

• Acute Disease
• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Mixed Phenotype Acute Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blinatumomab
1st cycle: 15 µg/m2/day as a 4 week continuous IV infusion for patients with a M1 marrow. For patients with a M2/M3 marrow a step-dosing strategy is required with a dose of 5 µg/m2/day in week 1 followed by 15 µg/m2/day in weeks 2, 3, and 4.
• Blinatumomab
2nd cycle: 15 µg/m2/day as a 4 week continuous iv infusion

Locations

Country	Name	City	State
Argentina	Hospital de Pediatría S.A.M.I.C. "Juan P. Garrahan"	Buenos Aires
Australia	Australian and New Zealand Children's Haematology/Oncology Group	Clayton	Victoria
Austria	St. Anna Children's Hospital	Vienna
Belgium	Hôpital Universitaire des Enfants Reine Fabiola	Brussel
Czechia	Hospital Motol V Uvalu 841	Prague
Denmark	AUH Skejby	Aarhus
Denmark	Copenhagen-Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense
Finland	New Children's Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	Oulu University Hospital	Oulu
Finland	Tampere University Hospital	Tampere
France	Hôpital Robert Debré, APHP	Paris
Germany	Universtitätsklinikum Eppendorf	Hamburg
Hungary	University of Pécs	Pécs
Ireland	National Children's Cancer Service	Dublin
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Roma
Japan	Osaka University Graduate School of Medicine 2-2	Osaka
Netherlands	Princess Máxima Center for pediatric oncology	Utrecht
Norway	St. Olavs Hospital	Trondheim
Portugal	Instituto Portugues de Oncologica Lisboa	Lisboa
Saudi Arabia	King Abdulaziz Medical City, King Abdullah International Medical Research Center	Riyadh
Sweden	Childrens Cancer Center Queen Silvia Children´s Hospital, Sahlgrenska University Hospital	Gothenburg

Sponsors (3)

Lead Sponsor	Collaborator
Princess Maxima Center for Pediatric Oncology	Amgen Europe B.V, University of Milano Bicocca

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Japan,  Netherlands,  Norway,  Portugal,  Saudi Arabia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival (EFS).	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.	5 years
Secondary	Overall survival	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.	8 years
Secondary	Endpoints by risk group	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.	8 years
Secondary	Outcome for the entire study cohort and according to risk group	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.	8 years
Secondary	Minimal Residual Disease	MRD response as defined in the protocol and frequencies of MRD levels	8 years
Secondary	CD19 (cluster of differentiation antigen 19) negative relapse	Proportion of CD19 negative relapses in the entire study cohort and according to risk group	8 years
Secondary	Myeloid lineage switches	Proportion of myeloid lineage switches in the entire study cohort and according to risk group	8 years
Secondary	Grade =3 adverse event	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.	8 years
Secondary	Grade =2 cardiac disorders	Proportion of grade =2 cardiac disorders at 2 and 5 years after diagnosis	5 years
Secondary	Overall survival after 1st relapse	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	8 years