Clinical trial NCT05327894: Interfant-21 Treatment Protocol for Infants Under 1 Year with KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia
Official title: Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year with KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia
Mixed Phenotype Acute Leukemia
Keywords: infant under one year
KMT2A-rearranged
Lead sponsor: Princess Maxima Center for Pediatric Oncology
Sponsor class: OTHER
Collaborators: name: University of Milano Bicocca
name: Amgen Europe B.V
First posted: 2022-04-14
Enrollment: 160
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Definition: Provide details about the Interventional Study Model. Limit: 1000 characters.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Event free survival (EFS).
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 8 years
measure: Endpoints by risk group
timeFrame: 8 years
measure: Outcome for the entire study cohort and according to risk group
timeFrame: 8 years
measure: Minimal Residual Disease
timeFrame: 8 years
measure: CD19 (cluster of differentiation antigen 19) negative relapse
timeFrame: 8 years
measure: Myeloid lineage switches
timeFrame: 8 years
measure: Grade ≥3 adverse event
timeFrame: 8 years
measure: Grade ≥2 cardiac disorders
timeFrame: 5 years
measure: Overall survival after 1st relapse
timeFrame: 8 years
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital de Pediatría S.A.M.I.C. "Juan P. Garrahan"
city: Clayton
country: Australia
facility: Australian and New Zealand Children's Haematology/Oncology Group
state: Victoria
city: Adelaide
country: Australia
facility: North Adelaide- Womens and Childrens Hospital
city: Clayton
country: Australia
facility: Monash Children's Hosptial
city: Parkville
country: Australia
facility: Royal Children's Hospital (Children's Cancer Centre)
city: Perth
country: Australia
facility: Perth Children's Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Sydney
country: Australia
facility: Sydney Childrens Hospital
city: Westmead
country: Australia
facility: The Childrens Hospital at Westmead
city: Vienna
country: Austria
facility: St. Anna Children's Hospital
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Brussel
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola
city: Citadelle Luik
country: Belgium
facility: Centre Hospitalier Regional De La Citadelle
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Montlegia Luik
country: Belgium
facility: CHC MontLegia
city: St Luc Sint-Lambrechts
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Olomouc
country: Czech Republic
facility: University Hospital Olomouc
city: Brno
country: Czechia
facility: University Hospital Brno
city: Prague
country: Czechia
facility: Hospital Motol V Uvalu 841
city: Aarhus
country: Denmark
facility: AUH Skejby
city: Copenhagen
country: Denmark
facility: Copenhagen-Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: New Children's Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Paris
country: France
facility: Hôpital Robert Debré, APHP
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin KöR
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Giessen
country: Germany
facility: Justus-Liebig-Universitaet Giessen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale) AöR
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Universtitätsklinikum Eppendorf
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein AöR
city: Munster
country: Germany
facility: Universitaetsklinikum Muenster AöR
city: Stuttgart
country: Germany
facility: Klinikum Der Landeshauptstadt Stuttgart gKAöR
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen AöR
city: Pécs
country: Hungary
facility: University of Pécs
city: Dublin
country: Ireland
facility: National Children's Cancer Service
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Ehime
country: Japan
facility: Ehime University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Hyogo
country: Japan
facility: Hyogo Prefectural Kobe Childrens Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Childrens Medical Center
city: Kyoto
country: Japan
facility: Kyoto Prefectural University of Medicine
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Mie
country: Japan
facility: Mie University Hospital
city: Nagoya
country: Japan
facility: Nagoya University Graduate School of Medicine
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka University Graduate School of Medicine 2-2
city: Saitama
country: Japan
facility: Saitama Prefectural Childrens Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka Childrens Hospital
city: Tohoku
country: Japan
facility: Tohoku University Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Childre&#39;s Medical Center
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Utrecht
country: Netherlands
facility: Princess Máxima Center for pediatric oncology
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Trondheim
country: Norway
facility: St. Olavs Hospital
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologica Lisboa
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City, King Abdullah International Medical Research Center
city: Bratislava
country: Slovakia
facility: National Institute of Children's Diseases
city: Barcelona
country: Spain
facility: Vall D'hebron Institut De Recerca
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Sevilla
country: Spain
facility: University Hospital Virgen Del Rocio S.L.
city: Valencia
country: Spain
facility: Hospital Universitario Y Politecnico La Fe
city: Gothenburg
country: Sweden
facility: Childrens Cancer Center Queen Silvia Children´s Hospital, Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: Linkoping University Hospital
city: Lund
country: Sweden
facility: Skane University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umea
country: Sweden
facility: Umea University Hospital
Study officials:
affiliation: Princess Maxima Center for Pediatric Oncology in The Netherlands
name: Janine Stutterheim, Dr
role: PRINCIPAL_INVESTIGATOR
References: