Treatment for Classical Hodgkin Lymphoma in Children and Adolescents

Study Overview
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Brief Summary
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Reduction of the indication for radiotherapy (RT) in newly diagnosed patients with classical Hodgkins lymphoma without compromising cure rates. Investigation of a chemotherapy intensification randomisation in intermediate and advanced classical Hodgkins lymphoma patients to compensate for reduction in RT.

Official Title
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An International, Multicentre, Randomised Controlled Trial. Treatment for Classical Hodgkin Lymphoma in Children and Adolescents Standard Treatment (Chemotherapy and RT) Compared With Experimental Treatment (Chemotherapy Without RT or Restricted to RT)

Conditions
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Classical Hodgkins Lymphoma in Children and Adolescents.

Intervention / Treatment
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* Radiation: Radiotherapy:
* Drug: Vincristine
* Drug: Etoposide
* Drug: Prednisone
* Drug: Doxorubicin
* Drug: Dacarbazine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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 Australia, France, Italy, New Zealand and United Kingdom 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: (Patients with one or more of the following criterion are excluded) prior chemotherapy or radiotherapy for other malignancies 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). 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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A-COPDAC-28<br>standard COPDAC-28 (chemotherapy cycle:Cyclophosphamide,Doxorubicin,Prednisone,Dacarbazine), chemotherapy and standard involved node radiotherapy. drugs: Prednisone 40mg/m2/day,P.O,day 1-day 15. Dacarbazine 250mg/m2, I.V. , infusion,day 1- day 3. Vincristine 15mg/m2 , I.V. , day1+day 8. Cyclophosphamide 500mg/m2,infusion,day 1+day 8. | Radiation: Radiotherapy:<br>* All patients will have 2 OPEAcycles(chemotherapy cycle:Vincristine,Etoposide,Prednisone,doxorubicin) ,After assignment ( by randomization) to one of the arms the patient will be treated accordingly . response assessment will be done after OPEA cycles (ERA) and after cycles of copdac 28 or DECOPDAC 21(LRA).according to the assessments results patients will have radiotherapy or not.<br>Drug: Vincristine<br>* ARM A and ARM B<br>Drug: Prednisone<br>* ARM A and ARM B , 40mg/m2/day p.o<br>Drug: Dacarbazine<br>* ARM A and ARM B , 250mg/m2 i.v<br>Drug: Cyclophosphamide<br>* ARM A and ARM B , 625mg/m2 i.v<br>|
| Experimental: B- DECOPDAC-21<br>DECOPDAC-21(chemotherapy cycle:Dacarbazine,Etoposide,Doxorubicin,Cyclophosphamide,Prednisone,Vincristine) intensified chemotherapy and no RT or restricted fields of radiotherapy. Drugs: Prednisone 40mg/m2/day,P.O,day 1-day 15: Dacarbazine 250mg/m2, I.V. , infusion,day 1- day 3 Vincristine 15mg/m2 , I.V. , day1+day 8 Cyclophosphamide 625mg/m2,infusion,day1+day2 Etoposide 100mg/m2/day,infusion,day 1- day 3 Doxorubicin 25mg/m2, infusion, day 1 | Radiation: Radiotherapy:<br>* All patients will have 2 OPEAcycles(chemotherapy cycle:Vincristine,Etoposide,Prednisone,doxorubicin) ,After assignment ( by randomization) to one of the arms the patient will be treated accordingly . response assessment will be done after OPEA cycles (ERA) and after cycles of copdac 28 or DECOPDAC 21(LRA).according to the assessments results patients will have radiotherapy or not.<br>Drug: Vincristine<br>* ARM A and ARM B<br>Drug: Etoposide<br>* ARM B , 100mg/m2/day<br>Drug: Prednisone<br>* ARM A and ARM B , 40mg/m2/day p.o<br>Drug: Doxorubicin<br>* ARM B , 25mg/m2<br>Drug: Dacarbazine<br>* ARM A and ARM B , 250mg/m2 i.v<br>Drug: Cyclophosphamide<br>* ARM A and ARM B , 625mg/m2 i.v<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase event free survival rate from 88% to 93% | Methods of measurement: chest X-ray; US neck, abdomen and pelvis; lung function; T4,Throid Stimulating Hormone ,US of thyroid; MRI of initially involved region; chest CT in patients with initial lung involvement. | Will be assessed once a year up to 5 years after end of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| comparison of haematotoxicity between arm A and arm B | Evaluation of haematotoxicity by documentation of blood count courses during OEPA, COPDAC-28 and DECOPDAC-21 cycles. Comparison between COPDAC-28 versus DECOPDAC-21. For ERA(early response assessment) PET(Positron Emission Tomography)-positive patients to compare to the LRA (late response assessment)PET-positivity rates after consolidation chemotherapy with COPDAC-28 or DECOPDAC-21. | Will be assessed in day 0,day 8,day 11,day 17 and day 21 of each cycle |