Clinical trial NCT02684708: Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents
Official title: European Network-Paediatric Hodgkin Lymphoma Study Group (EuroNet-PHL) Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Classical Hodgkin Lymphoma
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
name: Euronet Worldwide
First posted: 2016-02-18
Enrollment: 2200
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The EuroNet-PHL-C2 trial is an international, multicentre, randomised controlled trial with the aims to reduce the indication for radiotherapy in newly diagnosed patients with classical Hodgkin lymphoma without compromising cure rates and to investigate a chemotherapy intensification randomisation in intermediate and advanced classical Hodgkin lymphoma to compensate for reduction in radiotherapy.

Detailed description: EuroNet-PHL-C2 is a comprehensive treatment strategy for all first line classical Hodgkin Lymphoma (cHL) patients under 18 years (under 25 years in UK, Italy and France). The overall strategy is risk stratified (defining chemotherapy) and response adapted (defining radiotherapy) to tailor the amount of treatment to the individual patient and decrease long term complications.

* Radiotherapy indication will be restricted. Patients with a negative PET scan after two cycles of OEPA chemotherapy (Early Response Assessment - ERA) will not receive radiotherapy. The threshold for negative PET scan at ERA shifts from the previously used Deauville 1 and 2 = negative (as in the C1 trial) to Deauville 1, 2 and 3 = negative, thereby increasing the number of negative patients without indication for RT.
* Chemotherapy Randomisation

All intermediate (TL-2) and advanced stage (TL-3) patients will be randomised between respectively 2 or 4 standard COPDAC-28 or intensified DECOPDAC-21 consolidation chemotherapy cycles. To avoid delayed consolidation, randomisation has to be performed before ERA and as soon as the TL-assignment is confirmed by central review. Therefore two randomised sub-studies arise based on the ERA PET response:

Patients with adequate response at ERA do not receive radiotherapy - a randomised controlled chemotherapy comparison to show that intensified DECOPDAC-21 consolidation chemotherapy improves EFS as compared to standard COPDAC-28

Patients with inadequate response at ERA - a randomised controlled chemotherapy-radiotherapy comparison - to show that DECOPDAC-21 combined with radiotherapy restricted to sites that remain FDG-PET positive at the end of all chemotherapy (Late response assessment - LRA) has comparable EFS compared to COPDAC-28 plus standard involved node radiotherapy as in the C1 trial.

* Risk stratification is refined Former treatment groups (TG) of the EuroNet-PHL-C1 trial are reassigned into treatment levels (TL) by shifting early stage patients (former TG-1) with risk factors into TL-2.
* Semi-quantitative 'qPET' Results of semi-quantitative qPET are formally integrated into the response assessment.

Eligibility criteria: 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 specialized Teenage and Young Adult (TYA) units in France, Italy 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

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 month 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

Primary outcomes:
measure: Event-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Progression-free survival
timeFrame: 5 years
measure: CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis
timeFrame: 5 years
measure: Time from day of PET imaging until decision on response category at ERA or LRA, respectively
timeFrame: 5 years
measure: Time from last day of chemotherapy to first day of radiotherapy in patients with radiotherapy indication
timeFrame: 5 years
measure: Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle
timeFrame: 5 years
Other outcomes:
Locations:
city: Victoria Park
country: Australia
facility: Royal Children's Hospital and Monash Medical Centre Royal Children's Hospital
city: Wien
country: Austria
facility: St. Anna Kinderspital
city: Leuven
country: Belgium
facility: Paediatric haemato-oncology, University Hospitals of Leuven
city: Prague
country: Czechia
facility: Dpt. of Pediatric Hematology and Oncology, Faculty Hospital Motol
city: Copenhagen
country: Denmark
facility: Department of Pediatric Hematology/Oncology (5054) The Child and Youth Clinic, University Hospital of Copenhagen
city: Paris
country: France
facility: Service d'Oncohématologie, Hopital d'Ènfants Armand Trousseau
city: Giessen
country: Germany
facility: Justus Liebig University of Giessen
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital, Crumlin
city: Petach Tikva
country: Israel
facility: Tel Aviv University Schneider Children's Medical Center of Israel The Rina Zaizov Pediatric Hematology Oncology Division
city: Aviano
country: Italy
facility: Pediatric Radiotherapy and Youth Area Unit C.R.O. - Centro di Riferimento Oncologico IRCCS
city: Utrecht
country: Netherlands
facility: Princess Máxima Center for pediatric oncology
city: Auckland
country: New Zealand
facility: Starship Blood and Cancer Centre, Starship Children's Hospital
city: Oslo
country: Norway
facility: Department of Medical Oncology Oslo University Hospital
city: Kraków
country: Poland
facility: Head of Department of Pediatric Oncology and Hematology, Polish-American Pediatric Institute, Jagiellonian University Medical Faculty
city: Bratislava
country: Slovakia
facility: Clinic of Pediatric Oncology University Children's Hospital
city: Sevilla
country: Spain
facility: Sección de Onco-Hematología Pediátrica Hospital Universitario Virgen Macarena y Virgen del Rocío
city: Uppsala
country: Sweden
facility: Pediatric Hematology & Oncology Children´s University Hospital
city: Lausanne
country: Switzerland
facility: CHUV - Centre Hospitalier Universitaire Vaudois = LS, Départment femme - meré - enfant, Service de pédiatrie, Unité d'hématologie-oncologie pédiatrique
city: London
country: United Kingdom
facility: University College London Hospitals
Study officials:
affiliation: Justus-Liebig University of Giessen
name: Dieter Koerholz, MD
role: STUDY_CHAIR
References: