Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
EuroNet-PHL-C2
- NCT ID:
NCT02684708
Conditions
- Classical Hodgkin Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| cyclophosphamide, vincristine, prednisone, dacarbazine | CYC, VCR, PRED, DTIC | COPDAC-28 |
| cyclo, vcr, pred, dacarb,etop and doxo | CYC, VCR, PRED, DTIC, ETO, DOXO | DECOPDAC-21 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| COPDAC-28 | Active Comparator | 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 | - cyclophosphamide, vincristine, prednisone, dacarbazine
|
| DECOPDAC-21 | Experimental | 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 | - cyclo, vcr, pred, dacarb,etop and 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 |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Event-free survival |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Time from treatment start until relapse/progression, secondary malignancy or death |
Secondary Outcome Measures
| Measure: | Overall survival |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Time from treatment start until death |
| Measure: | Progression-free survival |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Time from treatment start until relapse/progression or death |
| Measure: | CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Toxicity assessment according to CTCAE v4.0 |
| Measure: | Time from day of PET imaging until decision on response category at ERA or LRA, respectively |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Quality of Imaging (CT,MRI and PET-CT) acquisition, |
| Measure: | Time from last day of chemotherapy to first day of radiotherapy in patients with radiotherapy indication |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Quality of chemo-and radiotherapy delivery |
| Measure: | Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle |
| Time Frame: | 5 years |
| Safety Issue: | |
| Description: | Quality of chemotherapy delivery |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | University of Giessen |
Last Updated
May 13, 2021
