Clinical trial • Not applicable • Oncology|Haematology
RITUXIMAB for B-cell acute lymphoblastic leukaemia (childhood)|B precursor acute lymphoblastic leukaemia (Bcp-ALL)
Not applicable trial of RITUXIMAB for B-cell acute lymphoblastic leukaemia (childhood)|B precursor acute lymphoblastic leukaemia (Bcp-ALL).
Overview
- Trial Therapeutic Area
- Oncology|Haematology
- Trial Disease
- B-cell acute lymphoblastic leukaemia (childhood)|B precursor acute lymphoblastic leukaemia (Bcp-ALL)
- Trial Stage
- Not applicable
- Drug Modality
- Monoclonal antibody|Peptide/protein/enzyme
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 07-06-2024
- First CTIS Authorization Date
- 08-12-2024
Trial design
Randomised, open-label, comparator arms include standard therapy (no additional peg-asparaginase / no rituximab) versus experimental arms: extended/additional doses of peg-asparaginase during ib phase; and, in a separate randomization for cd20+ patients, addition of rituximab to intensive chemotherapy. specific dosing schedules for the randomized arms are not specified in the ctis record.-controlled Not applicable trial in Croatia, Greece, Hungary and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Comparator arms include standard therapy (no additional Peg-asparaginase / no rituximab) versus experimental arms: extended/additional doses of Peg-asparaginase during IB phase; and, in a separate randomization for CD20+ patients, addition of rituximab to intensive chemotherapy. Specific dosing schedules for the randomized arms are not specified in the CTIS record.
- Biomarker Stratified
- True, biomarker: CD20 expression and MRD (strata include MRD >=0.1% with CD20 >=10% of residual blasts vs others)
- Target Sample Size
- 600
Stratification factors
- Age (>1 year at diagnosis)
- Risk group (Intermediate and High-risk pB-ALL defined by genetics and/or treatment response)
- Early treatment response / MRD (day 15 MRD for Bcp-ALL)
- Day 15 bone marrow MRD CD20 status (MRD >=0.1% and CD20 expression >=10% of residual blasts)
Eligibility
Recruits 600 paediatric patients.
- Pregnancy Exclusion
- Pregnant or breastfeeding patient
- Vulnerable Population
- Participants are children aged 1 to <18 years; informed consent to participate is required ("Informed consent to participate in ALL IC-BFM 2022 trial available"). The CTIS record marks vulnerable population selected but does not provide further details on assent or guardian consent procedures.
Inclusion criteria
- {"criterion_text":"- Age at diagnosis 1- <18 years.\n- 2. Start of induction therapy within the enrollment period of the trial: from December 1st, 2022 through December 31, 2028.\n- 3- Diagnosis of ALL ensured by all the diagnostic criteria defined in the protocol.\n- 4.Informed consent to participate in ALL IC-BFM 2022 trial available.\n- 5. Admission, diagnosis, and therapy performed by a center participating in the study.\n- 6. Urine βHCG is negative in female patient with childbearing potential."}
Exclusion criteria
- {"criterion_text":"- Positive HBV serology (hepatitis B surface (HBs) antigen positive and HBc antibody positive/HBs antibody negative) and TBC documentation.\n- Pregnant or breastfeeding patient\n- Known allergy or contraindication (based on SmPC) to both IMPs"}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary endpoint will be the minimum time from the randomization until the first event: non-response after HR2 consolidation block, relapse, second malignancy or death from any cause (EFS time).","definition_or_measurement_approach":"EFS time defined as time from randomization until first event (non-response after HR2 consolidation block, relapse, second malignancy or death from any cause)."}
Secondary endpoints
- {"endpoint_text":"- Time to death from any cause, measured from the time of randomization (survival time).\n- End of induction (day 33) and end of early intensification (day 78) MRD status.\n- Safety of rituximab in combination with intensive chemotherapy: -Death in CR will be compared between the two arms. -The rate of severe infections (CTC grade 3 to 5) during the treatment and until the end of chemotherapy will be compared between the two arms. -The rate of rituximab infusion reactions (total number and by severity of reactions) will be estimated. -The rate of intensive care unit admissions will be compared between the two arms.\n- -Occurrence of infections on the target list (presumably associated with rituximab) will be compared between the two arms: cytomegalovirus, progressive multifocal leukoencephalopathy and Herpes zoster. -Need for immunoglobulin substitution will be compared between the two arms. IgG level will be measured at day 0 and then by physician discretion, but at least once monthly until the end of intensive chemotherapy and once every 3 months during maintenance chemotherapy until reaching normal level w\n- Additional Researchs: -To determine the relationship between CD20 expression on ALL blasts (initially, day 15, day 33, day 78) and response to monoclonal antibody therapy. -To determine whether the administration of an anti-B cell monoclonal antibody limits the incidence of peg-asparaginase allergy occurrence.","definition_or_measurement_approach":"Survival: time from randomization to death. MRD status measured at day 33 and day 78 (by Flow-Cytometry). Safety endpoints include comparison of death in CR, rates of severe infections (CTC grade 3-5), rituximab infusion reactions (number and severity), ICU admissions. Infection outcomes include specific pathogens; IgG measured at day 0 and then at least monthly during intensive chemotherapy and every 3 months during maintenance until normal level. Additional research: CD20 expression on blasts measured at baseline, day 15, day 33, day 78 and correlated with response; evaluation of peg-asparaginase allergy incidence."}
Recruitment
- Planned Sample Size
- 600
- Recruitment Window Months
- 135
- Consent Approach
- Informed consent to participate is required ("Informed consent to participate in ALL IC-BFM 2022 trial available"). The record notes vulnerable paediatric population selection but does not provide details on assent procedures, who provides consent (parent/guardian) or available language versions of consent documents.
Methods
- Recruitment through participating centres (admission, diagnosis, and therapy performed by a center participating in the study).
- Enrollment restricted to patients starting induction therapy within defined enrollment period (Dec 1, 2022 through Dec 31, 2028).
Geography
- Total Number Of Sites
- 16
- Total Number Of Participants
- 775
Croatia
- Earliest CTIS Part Ii Submission Date
- 29-11-2024
- Latest Decision Or Authorization Date
- 13-01-2025
- Processing Time Days
- 45
- Number Of Sites
- 2
- Number Of Participants
- 100
Sites
- Site Name
- University Hospital Centre Zagreb
- Department Name
- Department of pediatric hematology and oncology
- Contact Person Name
- Izabela Kranjčec
- Contact Person Email
- izabela.kranjcec@gmail.com
- Site Name
- Children's Hospital Zagreb
- Department Name
- Department of pediatric hematology and oncology
- Contact Person Name
- Ernest Bilic
- Contact Person Email
- ernestbilic@gmail.com
Greece
- Earliest CTIS Part Ii Submission Date
- 04-12-2024
- Latest Decision Or Authorization Date
- 09-01-2025
- Processing Time Days
- 36
- Number Of Sites
- 7
- Number Of Participants
- 325
Sites
- Site Name
- Athens General Children's Hospital Panagioti And Aglaia Kyriakou
- Department Name
- Oncology Department Aglaia Kyriakou (OTAK)
- Contact Person Name
- Dimitrios Doganis
- Contact Person Email
- doganisd@gmail.com
- Site Name
- University General Hospital Of Heraklion
- Department Name
- Hematology-Oncology Children’s Clinic
- Contact Person Name
- Nikolaos Katzilakis
- Contact Person Email
- katzilaher@yahoo.gr
- Site Name
- Mitera S.A.
- Department Name
- Children's - Adolescent's Oncology Clinic
- Contact Person Name
- Eleni Kosmidi
- Contact Person Email
- helkos@yahoo.com
- Site Name
- Nosokomeio Paidon I Agia Sofia
- Department Name
- Department of Pediatric Hematology and Oncology (TAO)
- Contact Person Name
- Maria Ampatzidou
- Contact Person Email
- tao@paidon-agiasofia.gr
- Site Name
- Ippokratio General Hospital Of Thessaloniki
- Department Name
- Pediatric-Oncology Department
- Contact Person Name
- Evgenia Papakonstantinou
- Contact Person Email
- dongol@ippokratio.gr
- Site Name
- Nosokomeio Paidon I Agia Sofia
- Department Name
- Hematology - Oncology Unit, 1st Pediatric Clinic of Athens’ University (UnPOHem)
- Contact Person Name
- Antonios Kattamis
- Contact Person Email
- ankatt@med.uoa.gr
- Site Name
- University General Hospital Of Thessaloniki Ahepa
- Department Name
- 2nd Paediatric Clinic of Aristotle University of Thessaliniki /Paedriatic-Adolescent Haematology
- Contact Person Name
- Emmanouil Hatzipantelis
- Contact Person Email
- hatzip@auth.gr
Hungary
- Earliest CTIS Part Ii Submission Date
- 06-11-2024
- Latest Decision Or Authorization Date
- 08-12-2024
- Processing Time Days
- 32
- Number Of Sites
- 6
- Number Of Participants
- 250
Sites
- Site Name
- Semmelweis University
- Department Name
- Department of Pediatrics
- Contact Person Name
- Gábor Kovács
- Contact Person Email
- kovacs.gabor1@med.semmelweis.hu
- Site Name
- University Of Debrecen
- Department Name
- Department of Pediatrics
- Contact Person Name
- Csongor Kiss
- Contact Person Email
- kisscs@med.unideb.hu
- Site Name
- University Of Pecs
- Department Name
- Department of Pediatrics
- Contact Person Name
- Gábor Ottóffy
- Contact Person Email
- ottoffy.gabor@pte.hu
- Site Name
- Heim Pal Orszagos Gyermekgyogyaszati Intezet
- Department Name
- Department of Pediatrics
- Contact Person Name
- Krisztina Csanádi
- Contact Person Email
- kemenypalosztaly@gmail.com
- Site Name
- University Of Szeged
- Department Name
- Department of Pediatrics
- Contact Person Name
- Krisztina Míta Gábor
- Contact Person Email
- gaborkmita@gmail.com
- Site Name
- Borsod-Abauj-Zemplen Varmegyei Koezponti Korhaz Es Egyetemi Oktatokorhaz
- Department Name
- Department of Pediatrics
- Contact Person Name
- Ágnes Kelemen
- Contact Person Email
- kelemen.igyek@bazmkorhaz.hu
Slovenia
- Earliest CTIS Part Ii Submission Date
- 30-05-2024
- Latest Decision Or Authorization Date
- 18-12-2024
- Processing Time Days
- 202
- Number Of Sites
- 1
- Number Of Participants
- 100
Sites
- Site Name
- University Medical Center Ljubljana
- Department Name
- 00
- Contact Person Name
- 00 00
- Contact Person Email
- 000@gmail.com
Sponsor
Primary sponsor
- Full Name
- Semmelweis University
- Organisation Type
- Educational Institution
- Country Of Registered Address
- Hungary
Contract research organisations
- Name
- Coronis Research S.A.
- Responsibilities
- support in study startup and regulatory aspects site management, initiation, monitoring and close-out support in local pharmacovigilance activities
Third parties
- {"country":"Greece","full_name":"Coronis Research S.A.","duties_or_roles":"support in study startup and regulatory aspects site management, initiation, monitoring and close-out support in local pharmacovigilance activities","organisation_type":"Pharmaceutical company"}
- {"country":"Croatia","full_name":"University Hospital Centre Zagreb","duties_or_roles":"support in study startup and regulatory aspects site management, initiation, monitoring and close-out support in local pharmacovigilance activities","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Hungary","full_name":"University Of Debrecen","duties_or_roles":"support in study startup and regulatory aspects site management, initiation, monitoring and close-out support in local pharmacovigilance activities","organisation_type":"Educational Institution"}
- {"country":"Slovenia","full_name":"University Medical Center Ljubljana","duties_or_roles":"support in study startup and regulatory aspects site management, initiation, monitoring and close-out support in local pharmacovigilance activities","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- Riximyo 500 mg concentrate for solution for infusion
- Active Substance
- RITUXIMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- INFUSION
- Route
- INFUSION
- Authorisation Status
- Authorised (marketing authorisation EU/1/17/1184/003)
- Maximum Dose
- Max daily: 750 mg; Max total: 4500 mg
- Investigational Product Name
- Oncaspar 750 U/ml powder for solution for injection/infusion
- Active Substance
- PEGASPARGASE
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- INFUSION
- Route
- INFUSION
- Authorisation Status
- Authorised (marketing authorisation EU/1/15/1070/002)
- Maximum Dose
- Max daily: 2500 (unit: Other); Max total: 27500 (unit: Other)
- Combination Treatment
- Yes
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