Interfant-21 Treatment Protocol for Infants Under 1 Year with KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia
- Conditions
- Acute Lymphoblastic LeukemiaMixed Phenotype Acute Leukemia
- Interventions
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
- 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.
- ≤365 days of age at time of diagnosis of ALL
- Written informed consent of the parents or other legally authorized guardian of the patient according to local law and regulations.
- KMT2A-germline patients
- T-ALL
- Age > 365 days at the time of diagnosis
- Relapsed ALL
- 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:
- CD19 negative B-precursor ALL at diagnosis
- 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).
- Proven hypersensitivity to the active substance or any of the excipients in blinatumomab.
- 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.
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 (76)
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
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
St. Anna Children's Hospital
🇦🇹Vienna, Austria
Antwerp University Hospital
🇧🇪Antwerp, Belgium
Hôpital Universitaire des Enfants Reine Fabiola
🇧🇪Brussel, Belgium
Centre Hospitalier Regional De La Citadelle
🇧🇪Citadelle Luik, Belgium
Universitair Ziekenhuis Gent
🇧🇪Ghent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHC MontLegia
🇧🇪Montlegia Luik, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪St Luc Sint-Lambrechts, Belgium
University Hospital Olomouc
🇨🇿Olomouc, Czech Republic
University Hospital Brno
🇨🇿Brno, Czechia
Hospital Motol V Uvalu 841
🇨🇿Prague, Czechia
AUH Skejby
🇩🇰Aarhus, Denmark
Copenhagen-Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
New Children's Hospital
🇫🇮Helsinki, Finland
Kuopio University Hospital
🇫🇮Kuopio, Finland
Oulu University Hospital
🇫🇮Oulu, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Hôpital Robert Debré, APHP
🇫🇷Paris, France
Charite Universitaetsmedizin Berlin KöR
🇩🇪Berlin, Germany
Klinikum Dortmund gGmbH
🇩🇪Dortmund, Germany
Justus-Liebig-Universitaet Giessen
🇩🇪Giessen, Germany
Universitaetsklinikum Halle (Saale) AöR
🇩🇪Halle, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universtitätsklinikum Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Schleswig-Holstein AöR
🇩🇪Kiel, Germany
Universitaetsklinikum Muenster AöR
🇩🇪Munster, Germany
Klinikum Der Landeshauptstadt Stuttgart gKAöR
🇩🇪Stuttgart, Germany
Universitaetsklinikum Tuebingen AöR
🇩🇪Tuebingen, Germany
University of Pécs
🇭🇺Pécs, Hungary
National Children's Cancer Service
🇮🇪Dublin, Ireland
IRCCS Ospedale Pediatrico Bambino Gesù
🇮🇹Roma, Italy
Chiba University Hospital
🇯🇵Chiba, Japan
Ehime University Hospital
🇯🇵Ehime, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Hyogo Prefectural Kobe Childrens Hospital
🇯🇵Hyogo, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Kanagawa Childrens Medical Center
🇯🇵Kanagawa, Japan
Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Mie University Hospital
🇯🇵Mie, Japan
Nagoya University Graduate School of Medicine
🇯🇵Nagoya, Japan
Osaka City General Hospital
🇯🇵Osaka, Japan
Osaka University Graduate School of Medicine 2-2
🇯🇵Osaka, Japan
Saitama Prefectural Childrens Medical Center
🇯🇵Saitama, Japan
Shizuoka Childrens Hospital
🇯🇵Shizuoka, Japan
Tohoku University Hospital
🇯🇵Tohoku, Japan
National Center for Child Health and Development
🇯🇵Tokyo, Japan
The University of Tokyo Hospital
🇯🇵Tokyo, Japan
Tokyo Metropolitan Childre's Medical Center
🇯🇵Tokyo, Japan
Vilnius University Hospital Santaros Klinikos
🇱🇹Vilnius, Lithuania
Princess Máxima Center for pediatric oncology
🇳🇱Utrecht, Netherlands
Haukeland University Hospital
🇳🇴Bergen, Norway
St. Olavs Hospital
🇳🇴Trondheim, Norway
Instituto Portugues de Oncologica Lisboa
🇵🇹Lisboa, Portugal
King Abdulaziz Medical City, King Abdullah International Medical Research Center
🇸🇦Riyadh, Saudi Arabia
National Institute of Children's Diseases
🇸🇰Bratislava, Slovakia
Vall D'hebron Institut De Recerca
🇪🇸Barcelona, Spain
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
University Hospital Virgen Del Rocio S.L.
🇪🇸Sevilla, Spain
Hospital Universitario Y Politecnico La Fe
🇪🇸Valencia, Spain
Childrens Cancer Center Queen Silvia Children´s Hospital, Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Linkoping University Hospital
🇸🇪Linkoping, Sweden
Skane University Hospital
🇸🇪Lund, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
Umea University Hospital
🇸🇪Umea, Sweden