Optimization of the Primary Therapy for Patients With Hodgkin's Disease and Evaluation of PET

Study Overview
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Brief Summary
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Prognosis of patients with Hodgkin´s lymphoma (HL) has been improved significantly over the last decade. Therefore, the impact of treatment associated long-term toxicities and late effects such as second cancers increased. The purpose of this prospective multicenter trial is to show the feasibility of the treatment with ABVD alone in patients with limited stage (HL1) and intermediate stage (HL2) disease and of an intensified etoposide-free chemotherapy regimen for patients with advanced disease (HL3) including 18F-FDG-PET evaluation.

Detailed Description
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The aim in limited and intermediate stages is to reduce the toxicity by omitting the subsequent radiotherapy in patients with complete remission after ABVD chemotherapy. Patients with limited disease receive four cycles, patients with intermediate disease (according to the criteria of the German Hodgkin Study group, GHSG) receice six cycles of ABVD. In case of residual mass (> 1.5 cm), additional involved field irradiation is planned. The aim in advanced disease using BACOPP-D regimen which includes cyclophosphamide, adriamycin, dacarbazine, procarbazine, prednisolone, bleomycin and vincristine, is to reduce the hematological toxicity and the secondary leukemias by omitting etoposide (in comparison to the BEACOPP escalated regimen). All patients receive eight cycles of the BACOPP-D regimen. In case of residual mass (> 1.5 cm), additional involved field irradiation is planned. Additionally, we want to evaluate the CT- and PET-based remission status after chemotherapy and at final staging.

Official Title
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Optimization of the Primary Therapy for Patients With Hodgkin's Lymphoma and Evaluation of the Positron Emission Tomography (PET) as a Diagnostic Tool for Primary Staging and Assessment of the Effects of the Therapy

Conditions
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Hodgkin Disease

Intervention / Treatment
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* Drug: Combined chemotherapy (ABVD, BACOPP-D)
* Procedure: Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (HL1): Histologically confirmed Hodgkin´s Lymphoma (WHO Classification 1999) Classical Hodgkin Lymphoma: Nodular sclerosis (type 1 and 2) / Mixed type / Lymphocyte depleted type / Lymphocyte rich type Nodular lymphocyte-predominant Hodgkin Lymphoma Patients in stage: Clinical stage (CS) I without risk factors / CS II without risk factors Age between 16 and 75 Written informed consent Inclusion criteria (HL2): Histologically confirmed Hodgkin´s Lymphoma (WHO Classification 1999) Classical Hodgkin´s Lymphoma: Nodular sclerosis (type 1 and 2) / Mixed type / Lymphocyte depleted type / Lymphocyte rich type Nodular lymphocyte-predominant Hodgkin Lymphoma Patients in stage Clinical stage (CS) I,II A with risk factors: Large mediastinal tumor (>1/3 of the maximal diameter of the thoracic cavity) / Extranodal disease / Sedimentation rate ≥ 50 mm/h for patients without B-symptomes or ≥ 30 mm/h for patients with B-symptomes / ≥ 3 lymph node areas infiltrated with tumor cells Clinical stage (CS) II B with risk factors: Sedimentation rate ≥ 50 mm/h for patients without B-symptomes or ≥ 30 mm/h for patients with B-symptomes / ≥ 3 lymph node areas infiltrated with tumor cells Age between 16 and 75 Written informed consent Inclusion criteria (HL3): Histologically confirmed Hodgkin´s Lymphoma (WHO Classification 1999) Classical Hodgkin's Lymphoma (Hodgkin's desease): Nodular sclerosis (type 1 and 2) / Mixed type / Lymphocyte depleted type / Lymphocyte rich type Nodular lymphocyte-predominant Hodgkin Lymphoma Patients in stage Clinical stage (CS) II B with minimum one of the following risk factors: Large mediastinal tumor (≥1/3 of the maximal diameter of the thoracic cavity) / Extranodal disease Clinical stage (CS) III Clinical stage (CS) IV Age between 16 and 65 Written informed consent Exclusion Criteria (HL1, HL2 and HL3): Poor general condition not related to the lymphoma (ECOG perfomance status 3 or 4; Karnofsky Index < 50 %) Severe concomitant diseases: cardiac insufficiency (NYHA grade III or IV) / chronic respiratory insufficiency with hypoxemia / Hepatic insufficiency (cirrhosis, Hepatitis B or C / chronic renal insufficiency / HIV infection or other out-of-control infections / hematopoetic insufficiency (Leukocytes < 3000/µl; Thrombocytes < 100.000/µl / psychiatric diseases History of previous malignancy in the last 5 years Pregnancy Patients not likely to comply to the requirements stemming form the participation in the trial

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Combined chemotherapy (ABVD, BACOPP-D)|nan|
|Procedure: Radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Feasibility and acute toxicity of the therapy |  |  | 
| - The Free from Therapy Failure (FFTF) rate after one year |  |  | 
| - Event-Free Survival (EFS) rate and overall survival rate |  |  | 
| - Evaluation of the PET as a diagnostic tool for the primary tumor staging as well for assessment of the effects of the therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Evaluation of the quality of life of the patients during and after the therapy |  |  | 
| - Occurence of late toxicity after the end of the therapy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's Lymphoma, Chemotherapy, Radiation therapy, PET