Clinical Trials /

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

NCT02684708

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

DrugSynonymsArms
cyclophosphamide, vincristine, prednisone, dacarbazineCYC, VCR, PRED, DTICCOPDAC-28
cyclo, vcr, pred, dacarb,etop and doxoCYC, VCR, PRED, DTIC, ETO, DOXODECOPDAC-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

NameTypeDescriptionInterventions
COPDAC-28Active Comparatorcyclophosphamide, 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-21Experimentalpatients 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:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:5 years
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:5 years
Safety Issue:
Description:
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:Recruiting
Lead Sponsor:University of Giessen

Last Updated

April 6, 2020