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

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ClinicalTrials.gov Identifier: NCT02684708
Recruitment Status : Recruiting
First Posted : February 18, 2016
Last Update Posted : December 5, 2016
Sponsor:
Collaborators:
Deutsche Krebshilfe e.V., Bonn (Germany)
Euronet Worldwide
Information provided by (Responsible Party):
Prof. Dr. Christine Mauz-Körholz, University of Giessen

Tracking Information
First Submitted Date  ICMJE November 19, 2015
First Posted Date  ICMJE February 18, 2016
Last Update Posted Date December 5, 2016
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
Event-free survival [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02684708 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • Overall survival [ Time Frame: 5 years ]
  • Progression-free survival [ Time Frame: 5 years ]
  • CTC (common toxicity criteria) grading during any individual treatment element including assessment of osteonecrosis [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 5 years ]
    Quality of chemo-and radiotherapy delivery
  • Time from last dose of prednisone/prednisolone in OEPA to start of the first consolidation cycle [ Time Frame: 5 years ]
    Quality of chemotherapy delivery
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents
Official Title  ICMJE European Network-Paediatric Hodgkin Lymphoma Study Group (EuroNet-PHL) Second International Inter-Group Study for Classical Hodgkin Lymphoma in Children and Adolescents
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Classical Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: cyclophosphamide, vincristine, prednisone, dacarbazine
    28-day chemotherapy cycle
    Other Name: CYC, VCR, PRED, DTIC
  • Drug: cyclo, vcr, pred, dacarb,etop and doxo
    21-day chemotherapy cycle
    Other Name: CYC, VCR, PRED, DTIC, ETO, DOXO
Study Arms  ICMJE
  • 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
    Intervention: Drug: cyclophosphamide, vincristine, prednisone, dacarbazine
  • 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
    Intervention: Drug: cyclo, vcr, pred, dacarb,etop and doxo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 11, 2016)
2200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dieter Koerholz, MD 0049-641-985 ext 57921 dieter.koerholz@paediat.med.uni-giessen.de
Contact: Christine Mauz-Koerholz, MD 0049-641-985 ext 59524 christine.mauz-koerholz@paediat.med.uni-giessen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02684708
Other Study ID Numbers  ICMJE EuroNet-PHL-C2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Prof. Dr. Christine Mauz-Körholz, University of Giessen
Study Sponsor  ICMJE Prof. Dr. Christine Mauz-Körholz
Collaborators  ICMJE
  • Deutsche Krebshilfe e.V., Bonn (Germany)
  • Euronet Worldwide
Investigators  ICMJE
Study Chair: Dieter Koerholz, MD Justus-Liebig University of Giessen
PRS Account University of Giessen
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP