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

NCT ID: NCT02684708

Last Updated: 2024-02-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 2200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-01
• Study Completion Date: 2026-09-30

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.

Conditions

Classical Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

COPDAC-28

cyclophosphamide, vincristine, prednisone, dacarbazine; cyclophosphamide 500 mg/m2, per infusion on day 1 + 8; vincristine 1.5 mg/m2 intravenously (capping dose 2 mg) on day 1 + 8 and prednisone 40 mg/m2/day by mouth divided into 3 doses (capping dose 80 mg/day) on day 1 - 15 and dacarbazine 250 mg/m2 infusion on day 1 - 3

Group Type: ACTIVE_COMPARATOR

cyclophosphamide, vincristine, prednisone, dacarbazine

Intervention Type: DRUG

28-day chemotherapy cycle

DECOPDAC-21

patients with intermediate and advanced stages will be randomized after the induction therapy to receive either COPDAC-28 standard consolidation or the intensified DECOPDAC-21. cyclophosphamide dose augmented to 625 mg/m2 and adminstered per infusion on day 1 and day 2; vincristine dose not changed; prednisone 40 mg/m2/day by mouth on day 1 - 8 (no capping dose prescribed), i.e. dose-reduction; dacarbazine dose not changed; etoposide infusion100 mg/m2/day on day 1 - 3 and doxorubicine 25 mg/m2 per infusion on day 1as additional drugs in comparison to active comparator; cycle is administered as 21 days instead of 28 days-cycle for intensification

Group Type: EXPERIMENTAL

cyclo, vcr, pred, dacarb,etop and doxo

Intervention Type: DRUG

21-day chemotherapy cycle

Interventions

cyclophosphamide, vincristine, prednisone, dacarbazine

28-day chemotherapy cycle

Intervention Type: DRUG

cyclo, vcr, pred, dacarb,etop and doxo

21-day chemotherapy cycle

Intervention Type: DRUG

Other Intervention Names

CYC, VCR, PRED, DTIC; CYC, VCR, PRED, DTIC, ETO, DOXO

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

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsche Krebshilfe e.V., Bonn (Germany)

OTHER

Sponsor Role: collaborator

Euronet Worldwide

OTHER

Sponsor Role: collaborator

University of Giessen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dieter Koerholz, MD

Role: STUDY_CHAIR

Justus-Liebig University of Giessen

Locations

Royal Children's Hospital and Monash Medical Centre Royal Children's Hospital

Victoria Park, , Australia

St. Anna Kinderspital

Vienna, , Austria

Paediatric haemato-oncology, University Hospitals of Leuven

Leuven, , Belgium

Dpt. of Pediatric Hematology and Oncology, Faculty Hospital Motol

Prague, , Czechia

Department of Pediatric Hematology/Oncology (5054) The Child and Youth Clinic, University Hospital of Copenhagen

Copenhagen, , Denmark

Service d'Oncohématologie, Hopital d'Ènfants Armand Trousseau

Paris, , France

Justus Liebig University of Giessen

Giessen, , Germany

Our Lady's Children's Hospital, Crumlin

Dublin, , Ireland

Tel Aviv University Schneider Children's Medical Center of Israel The Rina Zaizov Pediatric Hematology Oncology Division

Petah Tikva, , Israel

Pediatric Radiotherapy and Youth Area Unit C.R.O. - Centro di Riferimento Oncologico IRCCS

Aviano, , Italy

Princess Máxima Center for pediatric oncology

Utrecht, , Netherlands

Starship Blood and Cancer Centre, Starship Children's Hospital

Auckland, , New Zealand

Department of Medical Oncology Oslo University Hospital

Oslo, , Norway

Head of Department of Pediatric Oncology and Hematology, Polish-American Pediatric Institute, Jagiellonian University Medical Faculty

Krakow, , Poland

Clinic of Pediatric Oncology University Children's Hospital

Bratislava, , Slovakia

Sección de Onco-Hematología Pediátrica Hospital Universitario Virgen Macarena y Virgen del Rocío

Seville, , Spain

Pediatric Hematology & Oncology Children´s University Hospital

Uppsala, , Sweden

CHUV - Centre Hospitalier Universitaire Vaudois = LS, Départment femme - meré - enfant, Service de pédiatrie, Unité d'hématologie-oncologie pédiatrique

Lausanne, , Switzerland

University College London Hospitals

London, , United Kingdom

Countries

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

References

Pabari R, McCarten K, Flerlage J, Lai H, Mauz-Korholz C, Dieckmann K, Palese M, Kaste S, Castellino SM, Kelly KM, Stoevesandt D, Kurch L. Hodgkin lymphoma involving the extra-axial CNS: an AHOD1331, PHL-C1, and PHL-C2 report from the COG and EuroNet-PHL. Blood Adv. 2024 Sep 24;8(18):4856-4865. doi: 10.1182/bloodadvances.2023012346.

Reference Type: DERIVED

PMID: 39058968 (View on PubMed)

Drechsel KCE, Pilon MCF, Stoutjesdijk F, Meivis S, Schoonmade LJ, Wallace WHB, van Dulmen-den Broeder E, Beishuizen A, Kaspers GJL, Broer SL, Veening MA. Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma: a review. Hum Reprod Update. 2023 Jul 5;29(4):486-517. doi: 10.1093/humupd/dmad002.

Reference Type: DERIVED

PMID: 36779325 (View on PubMed)

Related Links

https://www.clinicaltrialsregister.eu/ctr-search/search?query=EuroNet-PHL-C2

Hodgkin lymphoma treatment in children and adolescents

Other Identifiers

EuroNet-PHL-C2

Identifier Type: -

Identifier Source: org_study_id