Very Early FDG-PET/CT-response Adapted Therapy for Advanced Hodgkin Lymphoma (H11)

Study Overview
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Brief Summary
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The main objective of the trial is to show that doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-based response-adapted therapy for advanced-stage Hodgkin lymphoma, with treatment intensification (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) in case of a positive fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) after one cycle of ABVD, has non-inferior efficacy compared with the intensive BEACOPPesc regimen. A second objective is to assess the prognostic value of FDG-PET/CT after one cycle of BEACOPPesc.

Official Title
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Very Early FDG-PET/CT-response Adapted Therapy for Advanced Stage Hodgkin Lymphoma, a Randomized Phase III Non-inferiority Study of the EORTC Lymphoma Group

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: ABVD + FDG-PET/CT Scan treatment adaptation
* Drug: BEACOPPesc


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Previously untreated, histologically proven classical Hodgkin lymphoma Clinical stages III/IV (Ann Arbor) Age 18-60 WHO performance 0-2 Adequate organ function Patients of childbearing/reproductive potential should use adequate birth control measures during the whole duration of study treatment. Written informed consent according to ICH/EU Good Clinical Practice, and national/local regulations Exclusion criteria: Pregnancy or lactation Specific contraindications to BEACOPPesc therapy, including: Poorly controlled diabetes mellitus HIV infection, Chronic active hepatitis B and/or hepatitis C Concomitant or previous malignancies with the exception of basal cell skin tumors, adequately treated carcinoma in situ of the cervix and any cancer that has been in complete remission for >5 years Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

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 |
| --- | --- |
| Experimental: experimental arm<br>An experimental arm (early FDG-PET/CT-response adapted), where all patients are initially treated with a single cycle of ABVD. Very early FDG-PET/CT-negative patients continue on ABVD therapy to a total of six cycles. Very early FDG-PET/CT-positive patients receive 3 cycles of BEACOPPesc followed by another 3 cycles of BEACOPPesc. Mid-treatment evaluation is performed after 4 cycles. In case of treatment failure (less than partial remission (PR)), the patient goes off protocol treatment. Only patients with residual FDG-PET/CT-positive disease after chemotherapy will receive radiotherapy (36 Gy/18 fractions on the FDG-PET/CT-positive residual mass(es)). | Drug: ABVD + FDG-PET/CT Scan treatment adaptation<br> <br> Drug: BEACOPPesc<br> <br> |
| Active Comparator: standard arm<br>A standard arm, where patients are treated with four cycles of BEACOPPesc followed by 2 cycles of BEACOPPesc. FDG-PET/CT is performed after one cycle, but with no therapeutic consequences. Mid-treatment evaluation is performed after four cycles. In case of treatment failure (less than PR), the patient goes off protocol treatment. Only patients with residual FDG-PET/CT-positive disease after chemotherapy will receive radiotherapy (36 Gy/18 fractions on the FDG-PET/CT-positive residual mass(es)). | Drug: BEACOPPesc<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from treatment failure |  | 9 years after first patient in (FPI) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response at the end of therapy |  | 9 years after FPI | 
| Progression-free survival |  | 9 years after FPI | 
| Overall survival |  | 9 years after FPI | 
| Acute toxicity | Hematological toxicity (blood cell count) can be significant especially for patients who will receive BEACOPPesc . Bleomycine interstitial pneumonitis has been frequently reported and requires the immediate stop of further bleomycine administration. Rarely, procarbazine allergy and intolerance has been reported. Nausea & vomiting due to cyclophosphamide, doxorubicin, dacarbazine and procarbazine may be significant. Total reversible alopecia occurs in most cases. Escalated BEACOPP-related toxic deaths have been reported but do not exceed those observed with standard ABVD. | 9 years after FPI | 
| Long-term toxicity in terms of second malignancies, cardiovascular and pulmonary events |  | 9 years after FPI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced stage