International Study for Treatment of High Risk Childhood Relapsed ALL 2010

Официальное название

International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A Randomized Phase II Study Conducted by the Resistant Disease Committee of the International Berlin, Frankfurt, Münster (BFM) Study Group

Обзор

The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.

Подробное описание

Though survival of children with acute lymphoblastic leukemia (ALL) has considerably improved over the past few decades, relapsed ALL remains a leading cause of mortality in children with cancer. Risk has been defined by the International (I) Berlin, Frankfurt, Münster (BFM) Study Group (SG) based on duration of first remission, immunophenotype of malignant clone, and site of relapse. Patients classified as high risk (HR) by these criteria have poor response rates to standard induction therapy, high rates of subsequent relapse and require an allogeneic hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd remission. Over the last decade members of the I-BFM-SG have investigated the use of different combinations of conventional cytotoxic agents. Even with allo-HSCT, none of these approaches have improved outcome above 40%. Therefore, for HR patients there is a need to investigate the curative potential of new agents combined with systemic therapy. The proteasome inhibitor bortezomib has shown synergistic activity with acceptable toxicity when combined with corticosteroids, anthracyclines and alkylating agents in adult patients with cancer as well as with dexamethasone, doxorubicin, vincristine and polyethylene glycol (PEG) asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized phase II design. Induction is followed by conventional intensive consolidation. After termination of the trial patients may be subjected to an investigational window, before all of them receive allo-HSCT.

Вмешательства

• Препарат Bortezomib
  Patients randomised to the HR-B arm receive induction, consolidation with the modified ALL R3 protocol. In this arm, patients are randomized to receive Bortezomib together with the ALL R3 protocol during induction. Administration of Bortezomib: 1.3 mg/m2 as intravenous bolus or subcutaneously (SC, at the discretion of the treating physician) on days 1 and 4 of weeks 1 and 3.

Первичные конечные точки

• Rate of Complete Remission [Срок оценки: Week 4]

Вторичные конечные точки (7)

• Event-free Survival [Срок оценки: Year 3]
• Overall Survival [Срок оценки: Year 3]
• Minimal Residual Disease Reduction (MRD) [Срок оценки: Week 4]
• Minimal Residual Disease Load [Срок оценки: Week 15]
• Minimal Residual Disease (MRD) [Срок оценки: Week 15]
• Complete Remission/Minimal Residual Disease Rates During Consolidation [Срок оценки: Week 5, 8, 11, 15]
• Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC) [Срок оценки: At induction up to week 5]

Критерии участия

Критерии включения

• Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
• Children less than 18 years of age at date of inclusion into the study
• Meeting HR criteria any BM relapse, early/very early isolated BM relapse, very early isolated/combined extramedullary relapse)
• Patient enrolled in a participating centre
• Written informed consent
• Start of treatment falling into the study period
• No participation in other clinical trials 30 day prior to study enrolment that interfere with this protocol, except trials for primary ALL

Критерии исключения

• Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
• Pregnancy or positive pregnancy test (urine sample positive for β-humane choriongonadotropin (HCG) > 10 U/l)
• Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
• Breast feeding
• Relapse post allogeneic stem-cell transplantation
• Neuropathy > II°
• The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
• Objection to the study participation by a minor patient, able to object
• Any patient being dependent on the investigator
• No consent is given for saving and propagation of pseudonymized medical data for study reasons
• Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
• Subjects unwilling or unable to comply with the study procedures
• Subjects who are legally detained in an official institute

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Australian & New Zealand Childhood Hematology & Oncology Group — Clayton

Австрия · 1 центр

• St. Anna Kinderkrebsforschung, CCRI — Vienna

Бельгия · 1 центр

• Hòpital Universitaire des Enfants Reine Fabiola — Brussels

Чехия · 1 центр

• University Hospital Motol — Prague

Дания · 1 центр

• Copenhagen University Hospital (Rigshospitalet) — Copenhagen

Финляндия · 1 центр

• Turku University Central Hospital — Turku

Франция · 1 центр

• CHU Nice — Nice

Израиль · 1 центр

• Tel Aviv Sourasky Medical Centre — Tel Aviv

Италия · 1 центр

• Ospedale Pediatrico Bambino Gesù — Roma

Нидерланды · 1 центр

• Prinses Máxima Centrum, Lundlaan — Utrecht

Норвегия · 1 центр

• Oslo University Hospital — Oslo

Польша · 1 центр

• Dpt. SCT and Hematology/Oncology University Wroclaw — Wroclaw

Португалия · 1 центр

• Instituto Português de Oncologia de Lisboa — Lisbon

Швеция · 1 центр

• University Hospital Stockholm — Stockholm

Великобритания · 1 центр

• Royal Manchester Children's Hospital — Manchester

Идентификаторы

NCT: NCT03590171 · IntReALL HR 2010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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