E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute lymphoblastic leukemia in children |
Acute lymfatische leukemie bij kinderen |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To treat children with ALL with the best available treatment as possible, based upon the risk factors of the patient at diagnosis. |
Behandeling van kinderen met ALL volgens de best beschikbare therapie, rekening houdend met de aanwezigheid van risicofactoren bij diagnose. |
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E.2.2 | Secondary objectives of the trial |
Reduction of toxicity of treatment. Reduction of allergic reactions on chemotherapy. Reduction of infections during intensification of treatment. |
Reductie van toxiciteit van behandeling. Reductie van allergische reacties op chemotherapie. Reductie van optreden van infecties tijdens intensieve fase van behandeling. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Two randomisations: 1) randomisation for treatment with asparaginase in order to reduce allergic reactions/silent inactivation of asparaginase. 2) randomisation for treatment with immunoglobulines in order to reduce infections during treatment. |
Twee randomisaties: 1) Randomisaties voor behandeling met asparaginase om allergische reacties/silent inactivation te analyseren 2) Randomisatie voor behandeling met immuunglobulines om optreden infecties tijdens behandeling te reduceren. |
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E.3 | Principal inclusion criteria |
1. Newly diagnosed patients with T-lineage or precursor-B lineage ALL (patients with mature B-ALL are not eligible) 2. Age between ≥ 1 and < 19 years 3. Informed consent signed by parents/guardians and patient if 12 years or older 4. Diagnosis ALL confirmed by DCOG laboratory 5. Patient should be treated in a Dutch Childhood Oncology Centre 6. Patient should be >3 months settled in The Netherlands at diagnosis |
1. Nieuwe diagnose patienten met T- of preB ALL (patienten met mature B-ALL zijn niet eligible) 2. Leeftijd ≥ 1 en < 19 jaar 3. Informed consent getekend door ouders/verzorgers en patient als patient ≥ 12 jaar 4. Diagnose bevestigd door SKION laboratorium 5. Patient wordt behandeld in kinderoncologisch centrum in NL 6. Patient is minimaal >3 maanden woonachtig in NL |
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E.4 | Principal exclusion criteria |
1. Age ≥ 19 years at diagnosis 2. Age < 366 days at diagnosis (infant ALL); these patients are eligible for the Interfant protocol 3. Patients with secondary ALL 4. Patients with mature B-ALL (immunophenotypical or documented presence of karyotype t(8;14), t(2;8), t(8;22) and breakpoint as in B-ALL) 5. Patients with relapsed ALL 6. Pre-existing contra-indications for treatment according to (parts of) protocol ALL-11. 7. Essential data missing (in consultation with the protocol chairman) 8. Treatment with systemic corticosteroids and/or cytostatics in a 4-week interval prior to diagnosis. One exception is the use of corticosteroids as emergency treatment. 9. Patients with Ph-positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR/ABL fusion transcript). These patients will be transferred to the EsPhALL protocol in induction according to the guidelines of the EsPhALL protocol. |
1. Leeftijd ≥ 19 jaar bij diagnose 2. Leeftijd < 366 dagen bij diagnose (infant ALL), deze kinderen worden behandeld volgens Interfant protocol 3. secundaire ALL 4. Mature B-ALL (vastgesteld door immunophenotypering, danwel door karyotpye t(8;14), t(2;8), t(8;22) en breekpunt als bij B-ALL) 5. recidief ALL 6. pre-existente contra-indicaties voor behandeling met (delen) van protocol ALL-11 7.essentiele data missen 8. behandeling met systemische corticosteroiden en/of chemotherapie in de 4 weken voorafgaande aan diagnose. Uitzondering is het gebruik van corticosteroiden als ‘noodbehandeling’. 9. Ph-positieve ALL (aanwezigheid van t(9;22)(q34;q11) en/of aanw van de BCR-ABL fusieproduct) Deze patienten worden behandeld volgens EsPhALL-protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Primary endpoint is survival. 2. Primary endpoint is the number of allergic reactions/silent inactivation of asparaginase. 3. Primary endpoint is the number of infectious episodes for which patients are admitted to the hospital and receive therapeutic antibiotics or antifungals. 4. Primary endpoint is the number of patients with allergic reaction or silent inactivation to PEGasparaginase and who are therefore switched to Erwinase. |
1. Primaire eindpunt is survival. 2. primaire eindpunt is aantal allergische reacties/silent inactivation bij asparaginase. 3. Primaire eindpunt is het aantal infectieuze episodes voor patienten die opgenomen zijn in het ziekenhuis en therapeutisch antibiotica of antifungale therapie krijgen. 4. Primaire eindpunt is het aantal patienten met allergische reactie/silent inactivatie op PEG-asparaginase en om deze reden switch naar behandeling met Erwinase. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During interim analyses and also at the end of this protocol, expected in 2018. |
Gedurende interim analyses en aan het eind van dit protocol, verwachting 2018. |
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E.5.2 | Secondary end point(s) |
1. Secondary endpoints are EFS, CIR, death in induction, death in remission and toxicity. 2. Secondary endpoints are toxicity, EFS and survival. 3. Secondary endpoint is the average cumulative dose of PEGasparaginase administered to patients in the MR arm A compared to the historical control of the ALL-10 MR study.
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1. Secondaire eindpunten zijn EFS, CIR, overlijden in inductie, overlijden in remissie and toxiciteit. 2. Secondaire eindpunten zijn toxiciteit, EFS en overleving. 3. Secondaire eindpunt is de gemiddelde cummulatieve dosis van PEGasparaginase toegediend aan patienten in de MR arm A vergeleken met de historische controle van de ALL-10 MR studie. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During interim analyses and also at the end of this protocol, expected in 2018. |
Gedurende interim analyses en aan het eind van dit protocol, verwachting 2018. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Individual follow-up for 5 years after study entry is required for this protocol. Long-term follow-up is strongly recommended and will be organised according to Dutch guideline |
Iedere patient wordt 5 jaar lang gezien door de behandelend arts, hierna zal hij/zij via de lange termijn effecten poli (LATER) gevolgd worden. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |