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

Sponsor

University of Giessen (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02684708

Collaborator

Deutsche Krebshilfe e.V., Bonn (Germany) (Other), Euronet Worldwide (Other)

2,200

Enrollment

Locations

Arms

132

Duration (Months)

115.8

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma	Drug: cyclophosphamide, vincristine, prednisone, dacarbazine Drug: cyclo, vcr, pred, dacarb,etop and doxo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2015

Anticipated Primary Completion Date :

Sep 30, 2026

Anticipated Study Completion Date :

Sep 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: cyclophosphamide, vincristine, prednisone, dacarbazine 28-day chemotherapy cycle Other Names: CYC, VCR, PRED, DTIC
Experimental: 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	Drug: cyclo, vcr, pred, dacarb,etop and doxo 21-day chemotherapy cycle Other Names: CYC, VCR, PRED, DTIC, ETO, DOXO

Arm

Intervention/Treatment

Active Comparator: 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

Drug: cyclophosphamide, vincristine, prednisone, dacarbazine

28-day chemotherapy cycle

Other Names:

CYC, VCR, PRED, DTIC

Experimental: 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

Drug: cyclo, vcr, pred, dacarb,etop and doxo

21-day chemotherapy cycle

Other Names:

CYC, VCR, PRED, DTIC, ETO, DOXO

Outcome Measures

Primary Outcome Measures

Event-free survival [5 years]
Time from treatment start until relapse/progression, secondary malignancy or death

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Royal Children's Hospital and Monash Medical Centre Royal Children's Hospital	Victoria Park	Australia	3052
2	St. Anna Kinderspital	Wien	Austria	1090
3	Paediatric haemato-oncology, University Hospitals of Leuven	Leuven	Belgium	3000
4	Dpt. of Pediatric Hematology and Oncology, Faculty Hospital Motol	Prague	Czechia	15006
5	Department of Pediatric Hematology/Oncology (5054) The Child and Youth Clinic, University Hospital of Copenhagen	Copenhagen	Denmark	2100
6	Service d'Oncohématologie, Hopital d'Ènfants Armand Trousseau	Paris	France	75571
7	Justus Liebig University of Giessen	Giessen	Germany	35392
8	Our Lady's Children's Hospital, Crumlin	Dublin	Ireland	12
9	Tel Aviv University Schneider Children's Medical Center of Israel The Rina Zaizov Pediatric Hematology Oncology Division	Petach Tikva	Israel	49202
10	Pediatric Radiotherapy and Youth Area Unit C.R.O. - Centro di Riferimento Oncologico IRCCS	Aviano	Italy	33081
11	Princess Máxima Center for pediatric oncology	Utrecht	Netherlands	3508
12	Starship Blood and Cancer Centre, Starship Children's Hospital	Auckland	New Zealand	1142
13	Department of Medical Oncology Oslo University Hospital	Oslo	Norway	0424
14	Head of Department of Pediatric Oncology and Hematology, Polish-American Pediatric Institute, Jagiellonian University Medical Faculty	Kraków	Poland	30-663
15	Clinic of Pediatric Oncology University Children's Hospital	Bratislava	Slovakia	83340
16	Sección de Onco-Hematología Pediátrica Hospital Universitario Virgen Macarena y Virgen del Rocío	Sevilla	Spain	41071
17	Pediatric Hematology & Oncology Children´s University Hospital	Uppsala	Sweden	75185
18	CHUV - Centre Hospitalier Universitaire Vaudois = LS, Départment femme - meré - enfant, Service de pédiatrie, Unité d'hématologie-oncologie pédiatrique	Lausanne	Switzerland	1011
19	University College London Hospitals	London	United Kingdom	NW1 2PG