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Trial registered on ANZCTR


Registration number
ACTRN12618000069257
Ethics application status
Approved
Date submitted
13/12/2016
Date registered
17/01/2018
Date last updated
17/01/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
European Network-Paediatric Hodgkin Lymphoma Study Group: Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents
Scientific title
EuroNet-PHL-C2: international, multicentre, randomised controlled trial for the first line treatment of classical Hodgkin`s Lymphoma in children and adolescents to individualise treatment (risk stratified chemotherapy and response adapted radiotherapy) and decrease long-term complications.
Secondary ID [1] 290736 0
NCT02684708
Secondary ID [2] 290737 0
EUCTR2012-004053-88-BE
Universal Trial Number (UTN)
Trial acronym
EuroNet-PHL-C2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Classical Hodgkin Lymphoma 301316 0
Condition category
Condition code
Cancer 301070 301070 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are assigned to treatment levels (TL) according to stage, tumour size and blood ESR values.
Group 1: Treatment level 1
2 x 28 day cycles of OEPA chemotherapy (OEPA: Prednisone/Prednisolone: 60 mg/m2/day orally, on days 1-15 + Vincristine: 1.5 mg/m2 i.v., on day 1, 8 and 15 + Doxorubicin: 40 mg/m2 i.v., day 1 and 15 + Etoposide/Etopophos: 125 mg/m2 Etoposide; i.v., day 1 – 5)
Patients with an adequate response via PET scan (ie. PET Deauville Score of 1, 2 or 3), receive 1 x 28 day cycle of COPDAC28 (COPDAC28 = Prednisone/Prednisolone: 40 mg/m2/day orally, on days 1-15 + Dacarbazine 250 mg/m2 i.v., day 1 – 3 + Vincristine: 1.5 mg/m2 i.v., on day 1 and 8 + Cyclophosphamide 500 mg/m2, i.v., day 1 + 8), beginning 1-2 weeks post OEPA.
Patients with an inadequate response via PET scan (ie. PET Deauville Score of 4 or 5) will receive involved node radiotherapy to all initially involved sites (19.8 Gy in 11 fractions given at 1 fraction daily for 5 days per week (1.8 Gy per fraction)) at 2-4 weeks post OEPA.
There is no randomisation in TL-1.

Group 2: Treatment Level 2 and 3 with an adequate early PET Response
All patients receive 2 cycles of OEPA (as above).
Patients with an adequate response via PET scan undergo randomisation between COPDAC28 (standard therapy, as above) or DECOPDAC21 (experimental: 21 day cycles of Prednisone/Prednisolone 40 mg/m2/day, orally on days 1 – 8 + Dacarbazine 250 mg/m2 i.v., day 1 – 3 + Vincristine: 1.5 mg/m2 i.v., on day 1 and 8 + Cyclophosphamide 625 mg/m2, i.v., day 1 and 2 + Etoposide/Etopophos 100 mg/m2/day i.v. on day 1-3 + Doxorubicin
25 mg/m2 i.v. on day 1).
Patients in TL2 receive 2 cycles of COPDAC28 or DECOPDAC21 and patients in TL3 receive 4 cycles of COPDAC28 or DECOPDAC21. Patients do not receive radiotherapy.

Group 3: Treatment Level 2 and 3 with an inadequate Early PET Response
All patients receive 2 cycles of OEPA (as above).
Patients with an inadequate response via PET scan undergo randomisation between
COPDAC28 (standard therapy) or DECOPDAC21 (experimental), as above.
Patients in TL2 receive 2 cycles of COPDAC28 or DECOPDAC21 and patients in TL3 receive 4 cycles of COPDAC28 or DECOPDAC21.
Patients receiving COPDAC28 are followed with standard involved node radiotherapy to all initially involved sites (19.8 Gy in 11 fractions (1.8 Gy per fraction), and a boost (10 Gy in 5 fractions (2 Gy per fraction)) to late response assessment (LRA) FDG-PET positive residuals. Patients who receive the intensified DECOPDAC21 chemotherapy will also receive radiotherapy to LRA FDG-PET positive sites only (28.8 Gy in 16 fractions given at 1 fraction daily for 5 days per week (1.8 Gy per fraction).
Intravenous drugs will be administered in hospital. Participants and their families will be asked to complete a medication diary to record oral medication usage.
Intervention code [1] 296638 0
Treatment: Drugs
Intervention code [2] 296639 0
Treatment: Other
Comparator / control treatment
Active Comparator: COPDAC-28
Drugs and Dose: Cyclophosphamide 500 mg/m2,i.v., on day 1 + 8; vincristine 1.5 mg/m2 i.v., on day 1 and 8; prednisone 40 mg/m2/day orally on day 1 - 15; dacarbazine 250 mg/m2 i.v., on day 1-3.
Length of cycle: 28 days
Duration of treatment varies according to treatment level and the patient’s response (TL-2 COPDAC-28 arm, 16-20 weeks and TL-3 COPDAC-28 arm 20-24 weeks)
Control group
Active

Outcomes
Primary outcome [1] 300492 0
Event-free survival (EFS) defined as time from start of treatment until the first of the following events: progression/relapse of disease (assessed by histological confirmation of biopsy of suspected lesion), secondary malignancy or death from any cause.
Timepoint [1] 300492 0
5 years
Secondary outcome [1] 330090 0
Overall Survival: defined as time from start of treatment until death from any cause
Timepoint [1] 330090 0
5 years
Secondary outcome [2] 330092 0
Progression Free Survival: defined as time from start of treatment until progression/relapse of disease assessed by histological confirmation of biopsy of suspected lesion
Timepoint [2] 330092 0
5 years
Secondary outcome [3] 330102 0
Serious adverse event rates: Common toxicity criteria grading during any individual treatment element, including assessment of osteonecrosis, according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Timepoint [3] 330102 0
5 years

Eligibility
Key inclusion criteria
1. Histologically confirmed primary diagnosis of classical Hodgkin’s lymphoma
2. Patients under 18 years of age on the date of written informed consent (In specialised Teenage and Young Adult units in Australia, France, Italy, New Zealand and UK patients 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.
3. Written informed consent of the patient and/or the patient’s parents or guardian according to national laws
4. Negative pregnancy test within 2 weeks prior to starting treatment for female patients with childbearing potential.
Minimum age
No limit
Maximum age
24 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior chemotherapy or radiotherapy for other malignancies
2. Pre-treatment of Hodgkin’s lymphoma (except for steroid pre-phase to a maximum of 7-10 days for emergency treatment of a large mediastinal tumour)
3. Diagnosis of lymphocyte-predominant Hodgkin’s lymphoma
4. Other (simultaneous) malignancies
5. Contraindication or known hypersensitivity to study drugs
6. Severe concomitant diseases (e.g. immune deficiency syndrome)
7. Known HIV-positivity
8. Residence outside the participating countries where long term follow-up cannot be guaranteed
9. Pregnancy and/or lactation
10. Patients who are sexually active and are unwilling to use adequate contraception during therapy and for one month after last trial treatment
11. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by Fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation of patients between COPDAC-28 and DECOPDAC-21 is performed centrally with a modified minimisation procedure with stochastic component according to Pocock (1983) in a 1:1 proportion.
Randomisation will be balanced according to the following criteria:
1. TL (TL-2 versus TL-3)
2. Countries
3. Trial site
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
TL-1: Sample size of 431; >80% power to detect if the treatment strategy has 5 year EFS rates above 90%.
TL2 and 3 who have an adequate response at early response assessment: Sample size of 1345 patients; 84% power to detect an increase in 5-year EFS rates from 88% to 93% at a two-sided significance level of a = 5%.
TL2 and 3 who have an adequate response at early response assessment: Sample size 424; This study is aiming for comparable efficacy (EFS) with less toxicity. Assuming equality of EFS in both arms (log hazard ratio = 0) and a standard error of .26 there is > 84% power to show that arms are comparable.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 7109 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 7110 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 7111 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 7112 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [5] 7113 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [6] 7119 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [7] 7120 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [8] 7121 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 14869 0
3052 - Parkville
Recruitment postcode(s) [2] 14870 0
2031 - Randwick
Recruitment postcode(s) [3] 14871 0
2145 - Westmead
Recruitment postcode(s) [4] 14872 0
2305 - New Lambton
Recruitment postcode(s) [5] 14873 0
4101 - South Brisbane
Recruitment postcode(s) [6] 14879 0
5006 - North Adelaide
Recruitment postcode(s) [7] 14880 0
6008 - Subiaco
Recruitment postcode(s) [8] 14881 0
3168 - Clayton
Recruitment outside Australia
Country [1] 8479 0
Germany
State/province [1] 8479 0
Country [2] 8480 0
Austria
State/province [2] 8480 0
Country [3] 8481 0
New Zealand
State/province [3] 8481 0
Country [4] 8482 0
Belgium
State/province [4] 8482 0
Country [5] 8483 0
Czech Republic
State/province [5] 8483 0
Country [6] 8484 0
Denmark
State/province [6] 8484 0
Country [7] 8485 0
Finland
State/province [7] 8485 0
Country [8] 8486 0
France
State/province [8] 8486 0
Country [9] 8487 0
Hungary
State/province [9] 8487 0
Country [10] 8488 0
Ireland
State/province [10] 8488 0
Country [11] 8489 0
Israel
State/province [11] 8489 0
Country [12] 8490 0
Italy
State/province [12] 8490 0
Country [13] 8491 0
Netherlands
State/province [13] 8491 0
Country [14] 8492 0
Norway
State/province [14] 8492 0
Country [15] 8493 0
Poland
State/province [15] 8493 0
Country [16] 8494 0
Portugal
State/province [16] 8494 0
Country [17] 8495 0
Slovenia
State/province [17] 8495 0
Country [18] 8497 0
Spain
State/province [18] 8497 0
Country [19] 8498 0
Switzerland
State/province [19] 8498 0
Country [20] 8499 0
United Kingdom
State/province [20] 8499 0

Funding & Sponsors
Funding source category [1] 295167 0
Charities/Societies/Foundations
Name [1] 295167 0
My Room - Children's Cancer Charity
Address [1] 295167 0
SUITE 3, 400 HIGH STREET, KEW VIC 3101
Country [1] 295167 0
Australia
Primary sponsor type
University
Name
Justus Liebig University of Giessen
Address
Rudolf-Buchheim-Str. 23
35392 Giessen
Germany
Country
Germany
Secondary sponsor category [1] 293991 0
Other Collaborative groups
Name [1] 293991 0
Australia & New Zealand Children's Haematology/Oncology Group (ANZCHOG)
Address [1] 293991 0
27-31 Wright St
Clayton
VIC 3168
Australia
Country [1] 293991 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296517 0
RCH Human Research Ethics Committee
Ethics committee address [1] 296517 0
Research Ethics & Governance
The Royal Children's Hospital
Level 4, South Building
50 Flemington Road
Parkville Vic 3052
Ethics committee country [1] 296517 0
Australia
Date submitted for ethics approval [1] 296517 0
11/11/2015
Approval date [1] 296517 0
04/03/2016
Ethics approval number [1] 296517 0
HREC/15/RCHM/114
Ethics committee name [2] 299368 0
Ethics Commission of the Medical Faculty of the Martin-Luther-University Halle-Wittenberg
Ethics committee address [2] 299368 0
Ethics Committee of
the Medical Faculty of
the Martin-Luther-University Halle-Wittenberg
06097 Halle (Saale)
Ethics committee country [2] 299368 0
Germany
Date submitted for ethics approval [2] 299368 0
Approval date [2] 299368 0
18/02/2015
Ethics approval number [2] 299368 0
2015-12

Summary
Brief summary
This aim of this international, multicentre trial is to evaluate the safety and efficacy of a comprehensive first line treatment strategy for paediatric and adolescent patients with Classical Hodgkin Lymphoma (cHL).

Who is it for?
You may be eligible to join this study if you are aged less than 25 years and have a histologically confirmed primary diagnosis of classical Hodgkin’s lymphoma (cHL).

Study details
Based on risk factors at diagnosis, patient will be considered either low risk (TL-1), intermediate risk (TL-2) or advanced risk (TL-3) cHL. All patients initially receive 2 x 28 day cycles of the chemotherapy combination OEPA (Prednisone/Prednisolone, Vincristine, Doxorubicin and Etoposide/Etopophos). The response to OEPA treatment is measured using FDG-PET imaging and the next phase of treatment is determined. Treatment may include chemotherapy combinations called COPDAC-28 (consists of Prednisone/Prednisolone, Dacarbazine, Vincristine and Cyclophosphamide in a 28 day cycle) or DECOPDAC-21 (consists of Prednisone/Prednisolone, Dacarbazine, Vincristine and Cyclophosphamide, Etoposide/Etopophos and Doxorubicin in a 21 day cycle). Depending on risk level and response to treatment, patients may also be treated with Radiation Therapy.
Patients in TL-2 and TL-3 will be randomly allocated to receive either the standard chemotherapy arm (COPDAC-28) or the experimental intensified chemotherapy arm (DECOPDAC-21).

Patient response to therapy will be monitored using imaging and clinical exams for 5 years following completion of treatment. It is hoped that this study will maintain or improve survival while decreasing long term complications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 71126 0
Dr Leanne Super
Address 71126 0
Level 2 East Building,
Children’s Cancer Centre
The Royal Children’s Hospital
50 Flemington Road
Parkville, Victoria, 3052, AUS
Country 71126 0
Australia
Phone 71126 0
+61 3 9345 5612
Fax 71126 0
+61 3 9345 5510
Email 71126 0
leanne.super@rch.org.au
Contact person for public queries
Name 71127 0
Ms Allison Lamb
Address 71127 0
Level 2 East Building,
Children’s Cancer Centre
The Royal Children’s Hospital
50 Flemington Road
Parkville, Victoria, 3052, AUS
Country 71127 0
Australia
Phone 71127 0
+61 3 9345 4989
Fax 71127 0
+61 3 9345 5510
Email 71127 0
allison.lamb@rch.org.au
Contact person for scientific queries
Name 71128 0
Prof Michael Sullivan
Address 71128 0
Level 2 East Building,
Children’s Cancer Centre
The Royal Children’s Hospital
50 Flemington Road
Parkville, Victoria, 3052, AUS
Country 71128 0
Australia
Phone 71128 0
+61 3 9345 5820
Fax 71128 0
+61 3 9345 5510
Email 71128 0
michael.sullivan@rch.org.au

No information has been provided regarding IPD availability
Summary results
No Results