Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents

Classical Hodgkin Lymphoma Clinical Trial

Official title:

European Network-Paediatric Hodgkin Lymphoma Study Group (EuroNet-PHL) Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02684708
• Other study ID #: EuroNet-PHL-C2
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 1, 2015
• Est. completion date: September 30, 2026

Study information

• Verified date: February 2024
• Source: University of Giessen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2200
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• cyclophosphamide, vincristine, prednisone, dacarbazine
28-day chemotherapy cycle
• cyclo, vcr, pred, dacarb,etop and doxo
21-day chemotherapy cycle

Locations

Country	Name	City	State
Australia	Royal Children's Hospital and Monash Medical Centre Royal Children's Hospital	Victoria Park
Austria	St. Anna Kinderspital	Wien
Belgium	Paediatric haemato-oncology, University Hospitals of Leuven	Leuven
Czechia	Dpt. of Pediatric Hematology and Oncology, Faculty Hospital Motol	Prague
Denmark	Department of Pediatric Hematology/Oncology (5054) The Child and Youth Clinic, University Hospital of Copenhagen	Copenhagen
France	Service d'Oncohématologie, Hopital d'Ènfants Armand Trousseau	Paris
Germany	Justus Liebig University of Giessen	Giessen
Ireland	Our Lady's Children's Hospital, Crumlin	Dublin
Israel	Tel Aviv University Schneider Children's Medical Center of Israel The Rina Zaizov Pediatric Hematology Oncology Division	Petach Tikva
Italy	Pediatric Radiotherapy and Youth Area Unit C.R.O. - Centro di Riferimento Oncologico IRCCS	Aviano
Netherlands	Princess Máxima Center for pediatric oncology	Utrecht
New Zealand	Starship Blood and Cancer Centre, Starship Children's Hospital	Auckland
Norway	Department of Medical Oncology Oslo University Hospital	Oslo
Poland	Head of Department of Pediatric Oncology and Hematology, Polish-American Pediatric Institute, Jagiellonian University Medical Faculty	Kraków
Slovakia	Clinic of Pediatric Oncology University Children's Hospital	Bratislava
Spain	Sección de Onco-Hematología Pediátrica Hospital Universitario Virgen Macarena y Virgen del Rocío	Sevilla
Sweden	Pediatric Hematology & Oncology Children´s University Hospital	Uppsala
Switzerland	CHUV - Centre Hospitalier Universitaire Vaudois = LS, Départment femme - meré - enfant, Service de pédiatrie, Unité d'hématologie-oncologie pédiatrique	Lausanne
United Kingdom	University College London Hospitals	London

Sponsors (3)

Lead Sponsor	Collaborator
University of Giessen	Deutsche Krebshilfe e.V., Bonn (Germany), Euronet Worldwide

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Czechia,  Denmark,  France,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  New Zealand,  Norway,  Poland,  Slovakia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	Time from treatment start until relapse/progression, secondary malignancy or death	5 years
Secondary	Overall survival	Time from treatment start until death	5 years
Secondary	Progression-free survival	Time from treatment start until relapse/progression or death	5 years
Secondary	CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis	Toxicity assessment according to CTCAE v4.0	5 years
Secondary	Time from day of PET imaging until decision on response category at ERA or LRA, respectively	Quality of Imaging (CT,MRI and PET-CT) acquisition,	5 years
Secondary	Time from last day of chemotherapy to first day of radiotherapy in patients with radiotherapy indication	Quality of chemo-and radiotherapy delivery	5 years
Secondary	Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle	Quality of chemotherapy delivery	5 years

External Links

•   Hodgkin lymphoma treatment in children and adolescents