Second international study of classical Hodgkin lymphoma in children and adolescents (EuroNet-PHL-C2)

Australia, Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom (ICTRP)

ICTRP Studien-ID
EUCTR2012-004053-88 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
European Network of Paediatric Hodgkin Lymphoma Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents (EuroNet-PHL-C2) (BASEC)

Wissenschaftlicher Titel
EuroNet-Paediatric Hodgkin?s Lymphoma Group Second International Inter-Group Study for Classical Hodgkin?s Lymphoma in Children and Adolescents - EuroNet-PHL-C2 (ICTRP)

Öffentlicher Titel
EuroNet-Paediatric Hodgkin?s Lymphoma Group Second trial conducted by European experts in the field for treating Classical Hodgkin?s Lymphoma in Children and Adolescents (ICTRP)

Untersuchte Krankheit(en)
Hodgkin lymphoma in children and adolescents;Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Untersuchte Intervention

Product Name: Vincristine
Product Code: VCR
Pharmaceutical Form: Solution for injection
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7
Current Sponsor code: VCR
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 1-2

Product Name: Etoposide
Product Code: ETO
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ETOPOSIDE
Current Sponsor code: ETO
Other descriptive name: ETOPOSIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Deltison
Product Name: Deltison
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
Current Sponsor code: PRED
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Doxorubicin
Product Code: DOX
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
INN or Proposed INN: DOXORUBICIN
CAS Number: 23214-92-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Product Name: Cyclophosphamide
Product Code: CYC
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Current Sponsor code: CYC
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Dacarbazine
Product Code: DAC
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: DACARBAZINE
CAS Number: 4342-03-4
Current Sponsor code: DAC
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 1.4-10

Product Name: Vinblastine
Product Code: VBL
Pharmaceutical Form: Solution for injection
INN or Proposed INN: VINBLASTINE
C (ICTRP)

Studientyp
Interventional clinical trial of medicinal product (ICTRP)

Studiendesign
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: two or four intensified DECOPDAC-21 consolidation chemotherapy cycles Number of treatment arms in the trial: 3 (ICTRP)

Ein-/Ausschlusskriterien
Gender:
Female: yes
Male: yes

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 specialised Teenage and Young Adult (TYA) units in Australia, France, Italy,
New Zealand 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 2200
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

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 year 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


Primäre und sekundäre Endpunkte
Main Objective: Randomised
1.To increase event-free survival in ERA(early response assessment) PET-negative intermediate and advanced stage patients (TL-2 and TL-3) without radiotherapy by using intensified consolidation chemotherapy (DECOPDAC-21).

2.To demonstrate in ERA PET-positive TL-2 and TL-3 patients that the combination of intensified consolidation chemotherapy (DECOPDAC-21) plus restricted field RT to sites that remain FDG-PET positive at the late response assessment (LRA) is comparable to the standard consolidation chemotherapy (COPDAC-28) plus standard involved node radiotherapy.

Non-randomised
3.To further reduce the radiotherapy indication in early stage patients by increasing the threshold for a positive FDG PET scan at early response assessment (ERA) to Deauville 4+ while still preserving a 5 year EFS estimate at a target of 90% or above.
;Secondary Objective: 1.Evaluation of haematotoxicity by documentation of blood count courses during OEPA, COPDAC-28 and DECOPDAC-21 cycles and comparison between COPDAC-28 versus DECOPDAC-21.
2.For ERA PET-positive patients to compare the LRA PET-positivity rates after consolidation chemotherapy with COPDAC-28 or DECOPDAC-21.
;Primary end point(s): Primary efficacy endpoint
? Event-free survival (EFS) defined as time from start of treatment until the first of the following events:
- progression/relapse of disease
- secondary malignancy
- death from any cause;Timepoint(s) of evaluation of this end point: Descriptive data analyses will be performed annually checking data integrity, monitoring study performance quality endpoints as well as describing treatment related toxicities for the annual safety report.
The clinical board of EuroNet-PHL will decide on adequate measures in response to potential findings. The DMC may be consulted for independent guidance if there is a potential change in the risk-benefit analysis or lack of consensus in the clinical board.
Interim analyses on efficacy will be performed annually starting in year three after the start of accrual when a meaningful number of patients will be on study for more than one year.
(ICTRP)

Secondary end point(s): Secondary endpoints
? Efficacy: overall survival (OS), progression-free survival (PFS)
? Safety: CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis
? Quality:
- Time from day of PET imaging until decision on response category at ERA or LRA, respectively
- Time from last day of chemotherapy to first day of radiotherapy in patients with radiotherapy indication
- Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle
- Duration of chemotherapy
- Chemotherapy dose actually administered divided by scheduled total dose for each drug
- Discontinuation or substitution rate for each drug
- Time from FDG-Injection to start of PET acquisition
- Proportion of patients with enhanced FDG-uptake in brown fat under use of beta-blockers
- Average liver FDG-uptake at staging, ERA and LRA (reproducibility)
- Applied FDG-dose in relation to the EANM paediatric dosage card recommendation
- Applied radiation dose in low dose PET-CT (tube current, tube voltage and rotation time)
- Duration of radiotherapy, radiotherapy discontinuation rate
- Delivery of radiotherapy according to protocol guidelines;Timepoint(s) of evaluation of this end point: Descriptive data analyses will be performed annually checking data integrity, monitoring study performance quality endpoints as well as describing treatment related toxicities for the annual safety report.
The clinical board of EuroNet-PHL will decide on adequate measures in response to potential findings. The DMC may be consulted for independent guidance if there is a potential change in the risk-benefit analysis or lack of consensus in the clinical board.
Interim analyses on efficacy will be performed annually starting in year three after the start of accrual when a meaningful number of patients will be on study for more than one year. (ICTRP)

Registrierungsdatum
20.06.2018 (ICTRP)

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Kinderheilkunde und Jugendmedizin, dieter.koerholz@paediat.med.uni-giessen.de, 004964198543420, Universit?tsklinik Gie?en und Marburg GmbH - Standort Gie?en (ICTRP)

Sekundäre IDs
EuroNet-PHL-C2, final, 2012-004053-88-DE (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004053-88 (ICTRP)