E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hodgkin lymphoma in children and adolescents |
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E.1.1.1 | Medical condition in easily understood language |
Cancer which affects lymph nodes and lymphatic tissue in children and young people, named Hodgkin lymphoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Randomised 1. To increase event-free survival in ERA(early response assessment) PET-negative intermediate and advanced stage patients (TL-2 and TL-3) without radiotherapy by using intensified consolidation chemotherapy (DECOPDAC-21).
2. To demonstrate in ERA PET-positive TL-2 and TL-3 patients that the combination of intensified consolidation chemotherapy (DECOPDAC-21) plus restricted field RT to sites that remain FDG-PET positive at the late response assessment (LRA) is comparable to the standard consolidation chemotherapy (COPDAC-28) plus standard involved node radiotherapy.
Non-randomised 3. To further reduce the radiotherapy indication in early stage patients by increasing the threshold for a positive FDG PET scan at early response assessment (ERA) to Deauville 4+ while still preserving a 5 year EFS estimate at a target of 90% or above.
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Randomiserade frågeställningar 1. Att öka den sjukdomsfria överlevnaden hos patienter med intermediär och avancerad sjukdom (TL2-TL3) som är PET-negativa vid utvärdering av behandlingsresultat efter de först två behandlingsblocken (eRA) och därför inte får radioterapi, genom att ge intensifierad konsolideringskemoterapi med DECOPDAC-21.
2. Att visa för TL2-TL3 patienter som är eRA PET-positiva att kombinationen av intensifierad konsolideringskemoterapi med DECOPDAC-21 och radioterapi enbart mot områden som är PET-positiva vid LRA ger jämförbara resultat med standardkemoterapi (COPDAC-28) plus standard radioterapi mot alla initialt involverade lymfknuteområden.
Icke randomiserad frågeställning 3. Att ytterligare minska indikationen för radioterapi genom att höja tröskeln för PET-positivitet från Deuville 3 till Deuville 4 utan att EFS blir lägre än 90%. |
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E.2.2 | Secondary objectives of the trial |
1. Evaluation of haematotoxicity by documentation of blood count courses during OEPA, COPDAC-28 and DECOPDAC-21 cycles and comparison between COPDAC-28 versus DECOPDAC-21. 2. For ERA PET-positive patients to compare the LRA PET-positivity rates after consolidation chemotherapy with COPDAC-28 or DECOPDAC-21.
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1. Utvärdering av benmärgstoxicitet genom dokumentation av blodvärden vid kemoterapi med OEPA, COPDAC-28 och DECOPDAC-21 cykler för jämförelse mellan biverkningarna av COPDAC-28 och DECOPDAC-21 kemoterapi. 2. Att jämföra behandlingsresultaten efter avslutad kemoterapi med en tredje PET undersökning (LRA - late response assessment) hos patienter i TL2-3 som haft bra terapirespons vid eRA och därefter erhållit konsolideringsbehandling med COPDAC-28 eller DECOPDAC-21. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed primary diagnosis of classical Hodgkin’s lymphoma • Patients under 18 years of age on the date of written informed consent. In specialised Teenage and Young Adult (TYA) units in Australia, France, Italy, New Zealand and UK patients up to under 25 years of age can also be enrolled. Lower age limits will be country specific according to national laws or formal insurance requirements that may preclude very young patients. • Written informed consent of the patient and/or the patient’s parents or guardian according to national laws • Negative pregnancy test within 2 weeks prior to starting treatment for female patients with childbearing potential
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• Histologiskt konfirmerad primär diagnos klassiskt Hodgkins lymfom • Patienter yngre än 18 år då samtycke till deltagande i studien skrivs. På kliniker för tonåringar och unga vuxna i Australien, Frankrike, Italien, Nya Zeeland och Storbritannien kan patienter upp till 25 år inkluderas. Åldersgräns nedåt enligt nationella lagar eller enligt specifika försäkringskrav. • Skriftligt informerat samtycke från patienter och/eller patientens vårdnadshavare enligt nationella lagar •Negativt graviditetstest inom 2 veckor innan behandlingen startar för fertila kvinnor |
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E.4 | Principal exclusion criteria |
• Prior chemotherapy or radiotherapy for other malignancies • Pre-treatment of Hodgkin’s lymphoma (except for 7-10 days steroid pre-phase of a large mediastinal tumour) • Diagnosis of lymphocyte-predominant Hodgkin’s lymphoma • Other (simultaneous) malignancies • Contraindication or known hypersensitivity to study drugs • Severe concomitant diseases (e.g. immune deficiency syndrome) • Known HIV-positivity • Residence outside the participating countries where long term follow-up cannot be guaranteed • Pregnancy and/or lactation • Patients who are sexually active and are unwilling to use adequate contraception during therapy and for one year after last trial treatment • Current or recent (within 30 days prior to date of written informed consent) treatment with another investigational drug or participation in another interventional clinical trial |
• Tidigare kemo- eller radioterapi för andra maligniteter • Förbehandling av Hodgkins lymfom (förutom 7-10 dagar pre-fas med sterioder vid stor mediastinal tumör) • Patient diagnosticerad med lymfocytpredominant Hodgkins lymfom • Annan (samtidig) malignitet • Kontraindikation eller känd överkänslighet mot studieläkemedel • Samtidig allvarlig sjukdom (t ex immunbrist syndrom) • Känd HIV-positivitet • Boende i länder som inte deltar i studien där långtidsuppföljning inte kan garanteras • Graviditet/amning • Sexuellt aktiva patienter ovilliga att använda adekvat preventivmedel under behandlingen och ett år efter sista studiebehandlingen • Nuvarande eller nyligen (inom 30 dagar från skriftligt informerat samtycke) behandling med annat studieläkemedel eller deltagande i annan klinisk interventionsstudie
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint • Event-free survival (EFS) defined as time from start of treatment until the first of the following events: - progression/relapse of disease - secondary malignancy - death from any cause |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Descriptive data analyses will be performed annually checking data integrity, monitoring study performance quality endpoints as well as describing treatment related toxicities for the annual safety report. The clinical board of EuroNet-PHL will decide on adequate measures in response to potential findings. The DMC may be consulted for independent guidance if there is a potential change in the risk-benefit analysis or lack of consensus in the clinical board. Interim analyses on efficacy will be performed annually starting in year three after the start of accrual when a meaningful number of patients will be on study for more than one year.
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E.5.2 | Secondary end point(s) |
Secondary endpoints • Efficacy: overall survival (OS), progression-free survival (PFS) • Safety: CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis • Quality: - Time from day of PET imaging until decision on response category at ERA or LRA, respectively - Time from last day of chemotherapy to first day of radiotherapy in patients with radiotherapy indication - Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle - Duration of chemotherapy - Chemotherapy dose actually administered divided by scheduled total dose for each drug - Discontinuation or substitution rate for each drug - Time from FDG-Injection to start of PET acquisition - Proportion of patients with enhanced FDG-uptake in brown fat under use of beta-blockers - Average liver FDG-uptake at staging, ERA and LRA (reproducibility) - Applied FDG-dose in relation to the EANM paediatric dosage card recommendation - Applied radiation dose in low dose PET-CT (tube current, tube voltage and rotation time) - Duration of radiotherapy, radiotherapy discontinuation rate - Delivery of radiotherapy according to protocol guidelines |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Descriptive data analyses will be performed annually checking data integrity, monitoring study performance quality endpoints as well as describing treatment related toxicities for the annual safety report. The clinical board of EuroNet-PHL will decide on adequate measures in response to potential findings. The DMC may be consulted for independent guidance if there is a potential change in the risk-benefit analysis or lack of consensus in the clinical board. Interim analyses on efficacy will be performed annually starting in year three after the start of accrual when a meaningful number of patients will be on study for more than one year. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
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) | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
two or four intensified DECOPDAC-21 consolidation chemotherapy cycles |
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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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
Netherlands |
New Zealand |
Norway |
Poland |
Portugal |
Slovakia |
Slovenia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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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The recruitment period is expected to last six years (in Germany a maximum of five years for insurance reasons). The follow-up period will be five years after start of treatment. Individual trial participation ends with a last visit 60 months after start of treatment. After the individual end of study, the patients enter a follow-up observational protocol (outside the EuroNet-PHL-C2-trial). The EuroNet-PHL-C2-trial formally ends with the last visit of the last patient (=LVLS). |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |