Classical Hodgkin Lymphoma
Conditions
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.
Interventions
DRUGcyclophosphamide, vincristine, prednisone, dacarbazine
28-day chemotherapy cycle
DRUGcyclo, vcr, pred, dacarb,etop and doxo
21-day chemotherapy cycle
Sponsors
University of Giessen
Deutsche Krebshilfe e.V., Bonn (Germany)
Euronet Worldwide
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival | 5 years | Time from treatment start until relapse/progression, secondary malignancy or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia, Austria, Belgium, Czechia, Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Slovakia, Spain, Sweden, Switzerland, United Kingdom
Contacts
STUDY_CHAIRDieter Koerholz, MD
Justus-Liebig University of Giessen
Outcome results
None listed