HD21 for Advanced Stages

Study Overview
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Brief Summary
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Primary objective of the trial is to demonstrate non-inferior efficacy of six cycles of BrECADD compared to six cycles of escalated BEACOPP, each followed by radiotherapy to PET-positive residual lesions ≥2.5 cm, in terms of progression free survival (efficacy objective). If non-inferior efficacy can be shown, the co-primary objective is to further demonstrate reduced toxicity of the BrECADD treatment compared to the escalated BEACOPP treatment measured by treatment related morbidity (TRMorbidity objective).

Official Title
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HD21 for Advanced Stages Treatment Optimization Trial in the First-line Treatment of Advanced Stage Hodgkin Lymphoma; Comparison of 6 Cycles of Escalated BEACOPP With 6 Cycles of BrECADD

Conditions
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Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Bleomycin
* Drug: Etoposide
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Vincristine
* Drug: Procarbazine
* Drug: Prednisone
* Drug: Brentuximab Vedotin
* Drug: Dacarbazine
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven classical Hodgkin lymphoma First diagnosis, no previous treatment, 18 to 60 years of age Stage IIB with large mediastinal mass and/or extranodal lesions, stage III or IV Exclusion Criteria: Composite lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma Previous malignancy (exceptions: basalioma, carcinoma in situ of the cervix uteri, completely resected melanoma TNMpT1) Prior chemotherapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Active Comparator: BEACOPP<br>4 or 6 cycles of BEACOPP (21-day cycles) Bleomycin (B) Etoposide (E) Doxorubicin (A) Cyclophosphamide (C) Vincristine (O) Procarbazin (P) Prednisone (P). If FDG-PET is negative after two cycles patients will be given a total of four cycles. If FDG-PET is positive after two cycles patients will bev given a total of six cycles. | Drug: Bleomycin<br> <br> Drug: Etoposide<br> <br> Drug: Doxorubicin<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Vincristine<br> <br> Drug: Procarbazine<br> <br> Drug: Prednisone<br> <br> |
| Experimental: BRECADD<br>4 or 6 cycles of BRECADD (21.day cycles) Brentuximab Vedotin (BR) Etoposide (E) Cyclophosphamide (C) Doxorubicin (A) Dacarbazine (D) Dexamethasone (D). If FDG-PET is negative after two cycles patients will be given a total of four cycles. If FDG-PET is positive after two cycles patients will be given a total of six cycles. | Drug: Etoposide<br> <br> Drug: Doxorubicin<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Brentuximab Vedotin<br> <br> Drug: Dacarbazine<br> <br> Drug: Dexamethasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 5 years | 
| Treatment Related Morbidity |  | during 6 cycles of chemotherapy (21-day cycles) |