Bendamustine Study in Classical Hodgkin Lymphoma Patients Over 60 Treated by Prednisone, Vinblastine and Doxorubicin

Study Overview
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Brief Summary
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This study evaluates bendamustine in patients aged over 60 years with classical Hodgkin Lymphoma treated by prednisone, vinblastine and doxorubicin. 90 patients will be enrolled in this study.

Detailed Description
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The usual treatment for Hodgkin lymphoma is chemotherapy Adriamycin (also known as doxorubicin) + Bleomycin + Vinblastine + Dacarbazine (ABVD). Studies have shown that patients aged over 60 years have a lower tolerance and efficiency during this treatment than younger patients. There are particular pulmonary toxicities with bleomycin included in the ABVD treatment. Alternative treatment strategies have been proposed removing bleomycin in the Prednisone + Vinblastine + Adriamycin/Doxorubicin +Gemcitabine (PVAG) protocol evaluated in more than 60 patients. Compared to ABVD treatment, PVAG treatment presented a more favorable toxicity profile. The quality of response between the two treatments is substantially equal. Bendamustine was evaluated in four studies in patients with Hodgkin lymphoma in relapse and showed higher efficacy than gemcitabine with an acceptable toxicity profile. In this study, the Sponsor and the coordinating investigator propose to replace dacarbazine in the standard ABVD protocol by bendamustine and to stop using bleomycin. The main objective of this study is to evaluate the safety and efficacy of bendamustine in patients treated with prednisone, vinblastine and doxorubicin. This is the PVAB treatment with which LYSARC and the coordinating investigator expect better tolerability and quality response.

Official Title
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A Prospective Phase II Study of Bendamustine in Patients Aged Over 60 Years With Classical Hodgkin Lymphoma Treated by Prednisone, Vinblastine and Doxorubicin

Conditions
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Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Bendamustine
* Drug: Prednisone
* Drug: Vinblastine
* Drug: Doxorubicin


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 the World Health Organization (WHO) criteria excluding nodular lymphocyte predominant subtype Age of 61 years or older No previous treatment for Hodgkin lymphoma Ann Arbor stages: II with mediastinum/thorax ≥0.33 or extranodal localization and with B symptoms Or III Or IV Baseline 18-FluoroDeoxyGlucose (FDG) PET scan (PET0) performed before any treatment with at least one hypermetabolic lesion Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate cardio-pulmonary function with Left Ventricular Ejection Fraction (LVEF) ≥ 50% Adequate renal function with creatinine clearance ≥ 40 mL/mn (MDRD formula) For patients aged 70 years old and more, a Mini Nutritional Assessment (MNA) ≥ 17 A minimum life expectancy of 3 months Negative Human Immunodeficiency Virus, Hepatitis B (HB) Virus (anti-HB c negativity) and Hepatitis C Virus serologies tests ≤ 30 days before inclusion (except after vaccination) Having previously signed a written informed consent The patient must be covered by a social security system, if applicable Men patient must agree to use an adequate method of contraception during the study treatment and until 6 months after the end of the study treatment. Exclusion Criteria: Any other type of lymphoma including nodular lymphocyte predominant subtype Any history of treated Hodgkin lymphoma Contra-indication to any drug contained in the chemotherapy regimens Any serious active disease (according to the investigator's decision) Poor hepatic function (total bilirubin level > 30 μmol/L or transaminases > 2.5 maximum normal level) unless these abnormalities are related to the lymphoma Poor bone marrow reserve as defined by leukocytes < 2 G/L or platelets < 100 G/L, unless related to bone marrow infiltration Any history of cancer during the last 3 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. Patients previously diagnosed with prostate cancer are eligible if they fulfil all the followings: their disease was T1-T2a, N0, M0, with a Gleason score ≤ 7, and a prostate specific antigen (PSA) ≤ 10 ng/mL prior to initial therapy, they had definitive curative therapy (i.e. prostatectomy or radiotherapy) ≥ 2 years before Day 1 of Cycle 1, at a minimum 2 years following therapy, they had no clinical evidence of prostate cancer and their PSA was undetectable if they underwent prostatectomy or < 1 ng/mL if they did not undergo prostatectomy Severe metabolic disease interfering with normal application of protocol treatment as uncontrolled diabetes mellitus leading to impossibility to perform PET scan Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study Adult under tutelage

Ages Eligible for Study
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Minimum Age: 61 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PVAB regimen<br>Prednisone 40 mg/m2 (PO) Days 1-5 ; Vinblastine 6 mg/m2 (IV) Day 1 ; Doxorubicin 40 mg/m2 (IV) Day 1 ; Bendamustine 120 mg/m2 (IV) Day 1 | Drug: Bendamustine<br>* Bendamustine 120 mg/m2 (IV) Day 1<br>* Other names: LEVACT;Drug: Prednisone<br>* Prednisone 40 mg/m² PO<br>* Other names: CORTANCYL;Drug: Vinblastine<br>* Vinblastine 6 mg/m² IV<br>* Other names: VELBE;Drug: Doxorubicin<br>* Doxorubicin 40 mg/m² IV<br>* Other names: ADRIBLASTINE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Metabolic Response rate at the end of study treatment (after 6 cycles of study treatment or at premature treatment discontinuation) defined according to Lugano Classification | Complete Metabolic Response rate at the end of study treatment (after 6 cycles of study treatment or at premature treatment discontinuation) defined according to Lugano Classification | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the protocol, with adequate protocol adherence (adequate dose without excessive delay) | Feasibility of the protocol, with adequate protocol adherence (adequate dose without excessive delay) | 5 years | 
| Safety profile including immediate toxicities and non-tumor events | Safety profile including immediate toxicities and non-tumor events | 5 years | 
| Progression-free survival | Progression-free survival | 5 years | 
| Disease-free survival | Disease-free survival | 5 years | 
| Overall survival | Overall survival | 5 years | 
| Geriatric assessment program | 7 Quality of Life Questionnaires (QLQ) | 5 years |