Study of a Treatment Driven by Early PET Response to a Treatment Not Monitored by Early PET in Patients With AA Stage 3-4 or 2B HL

Study Overview
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Brief Summary
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All study treatments have proven efficacy in the treatment in Hodgkin lymphoma (HL). It is hoped that patients will achieve a good response to both induction therapies consisting either of 4 cycles of BEACOPPesc (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone) or 2 cycles of BEACOPPesc plus 2 cycles of ABVD (Adriamycine, Bléomycine, Vinblastine, Décarbazine). The use of F-FDG Position Emission Tomography performed after 2 cycles of chemotherapy (PET2) in the experimental arm will help to stratify patients in order to restrict the BEACOPPesc therapy continuation to those patients who achieved only a partial response after 2 BEACOPPesc regimen and to allow a conventional dose ABVD chemotherapy strategy for PET2 negative patients. For all patients included in the trial the achievement of a good response to induction treatment will be checked after four cycles of induction treatment including a centrally reviewed PET assessment Patients will be randomized after verification of eligibility and before the start of the protocol treatment.Patients will be randomly assigned to the standard treatment arm not monitored by early PET, or the experimental treatment arm driven by the PET2 result.

Official Title
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Randomized Phase III Study of a Treatment Driven by Early PET Response Compared to a Treatment Not Monitored by Early PET in Patients With Ann Arbor Stage III-IV or High Risk IIB Hodgkin Lymphoma

Conditions
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Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: BEACOPPesc
* Drug: BEACOPPesc - ABVD - PET2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with a first diagnosis of classical Hodgkin lymphoma according to world health organization (WHO) criteria excluding nodular lymphocyte predominant subtype Age of 16 to 60 years No previous treatment for Hodgkin lymphoma Ann Arbor stages: IIB with mediastinum/thorax ≥0.33 or extra nodal localization III IV Baseline 18-FDG PET scan (PET0)(F-FDG Positon Emission Tomography) performed before any treatment with at least one hypermetabolic lesion Eastern Cooperative Oncology Group (ECOG) performance status < 3 With a minimum life expectancy of 3 months Having previously signed a written informed consent The patient must be covered by a social security system (in France) Exclusion Criteria: Pregnant or lactating women Men and women of childbearing potential not practicing an adequate method of contraception during the study treatment and at least 3 months after the last study drug administration Any history of cancer or cancer treatment during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma Uncontrolled infectious disease, including active HBV (hepatitis B virus) infection defined by either detection of HBs Antigen or presence of anti HBs antibody without detectable anti HBc antibody. HIV (Human immunodeficiency virus), HCV (hepatitis C virus) or HTLV (Human T-lymphotropic virus) serology positivity Abnormal liver (bilirubin > 2,5 N) function unless abnormalities are due to AHL 2011 Protocol Version n°1.2_ 09/02/11_approved on March 11, 2011 EudraCT n°2010-022844-19 4 / 73 Hodgkin lymphoma Abnormal renal (Creatinin > 150 μmol/L) function unless abnormalities are due to Hodgkin lymphoma Leukopenia < 2 G/l or thrombopenia <100 G/l unless abnormalities are due to Hodgkin lymphoma Severe cardio-pulmonary, or metabolic disease interfering with normal application of protocol treatment: Left Ejection Ventricular Fraction <50% Respiratory insufficiency prohibiting bleomycin use Uncontrolled diabetes mellitus leading to impossibility to perform PET scan Impossibility to perform a baseline PET (PET0) before randomization and treatment beginning Incapable person

Ages Eligible for Study
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Minimum Age: 16 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

Allocation: Randomized
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard arm<br>Induction treatment: Patients will be treated by a BEACOPPesc regimen every 3 weeks for 4 cycles. A PET will be performed after 2 cycles of chemotherapy (PET2) with no decisional value, and after 4 cycles with decisional value. Consolidation treatment: depends on the reviewed PET4 result. In case of PET4 negative result, patient will received 2 additional cycles of BEACOPPesc, whatever the result of the PET2. In case of PET4 positive, the patient will be considered in treatment failure and proposed to a salvage therapy after pathologic confirmation of failure by biopsy of the hypermetabolic residual mass when possible. | Drug: BEACOPPesc<br> <br> |
| Experimental: Experimental arm<br>Induction treatment: Patients will be treated by a BEACOPPesc regimen every 3 weeks for 2 cycles followed by a PET scan (PET2). After PET2 central review: In case of positive PET2, the induction treatment will be completed by 2 additional cycles of BEACOPPesc In case of negative PET2, the induction treatment will be completed by 2 cycles of ABVD delivered every 4 weeks. The first cycle of ABVD will start at day 21 of the second cycle of BEACOPPesc. Consolidation treatment: depends on the reviewed PET4 result In case of PET4 negative result, consolidation treatment will depends on PET2 results: If PET2 was positive, patient will received 2 additional cycles of BEACOPPesc delivered every 3 weeks If PET2 was negative, patient will received 2 additional cycles of ABVD delivered every 4 weeks In case of PET4 positive, the patient will be considered as treatment failure. | Drug: BEACOPPesc - ABVD - PET2<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Evaluate by PFS at 5 years the non-inferiority of a chemotherapy of a therapeutic strategy driven by PET with a ABVD conventional dose chemotherapy for patients reaching a negative PET after 2 cycles of BEACOPPesc, compared to a treatment not monitored by early PET delivering 6 cycles of BEACOPPesc. | 5 years |