Clinical trial NCT02414568: Bendamustine Study in Classical Hodgkin Lymphoma Patients Over 60 Treated by Prednisone, Vinblastine and Doxorubicin
Official title: A Prospective Phase II Study of Bendamustine in Patients Aged Over 60 Years With Classical Hodgkin Lymphoma Treated by Prednisone, Vinblastine and Doxorubicin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Classical Hodgkin Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2015-04-10
Enrollment: 90
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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:

  1. 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,
  2. they had definitive curative therapy (i.e. prostatectomy or radiotherapy) ≥ 2 years before Day 1 of Cycle 1,
  3. 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

Primary outcomes:
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: Feasibility of the protocol, with adequate protocol adherence (adequate dose without excessive delay)
timeFrame: 5 years
measure: Safety profile including immediate toxicities and non-tumor events
timeFrame: 5 years
measure: Progression-free survival
timeFrame: 5 years
measure: Disease-free survival
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Geriatric assessment program
timeFrame: 5 years
Other outcomes:
Locations:
city: Bruges
country: Belgium
facility: A. Z. Sint-Jan
city: Bruxelles
country: Belgium
facility: Clinique Universitaire St Luc
city: Liège
country: Belgium
facility: CHU de Liège
city: Yvoir
country: Belgium
facility: UCL Mont Godinne
city: Amiens
country: France
facility: CHU d'Amiens - Groupe Hospitalier Sud
city: Besancon
country: France
facility: Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: CHRU de Brest - Hôpital Morvan
city: Caen
country: France
facility: CHU de Caen
city: Challes les eaux
country: France
facility: Médipôle de Savoie
city: Corbeil Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hôpital d'Enfants
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: La Roche sur Yon
country: France
facility: CH Départemental Vendée
city: Le Chesnay
country: France
facility: CH de Versailles
city: Le Mans
country: France
facility: CH du Mans
city: Lille
country: France
facility: CHRU de Lille
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Metz
country: France
facility: CHR de Metz-Thionville - Hôpital de Mercy
city: Montpellier
country: France
facility: Hôpital Lapeyronie
city: Mulhouse
country: France
facility: CH de Mulhouse
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nîmes
country: France
facility: CHRU de Nîmes
city: Paris
country: France
facility: Hôpital de la Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Necker
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Poitiers
country: France
facility: CHU Poitiers
city: Pontoise
country: France
facility: CH Rene Dubos
city: Pringy
country: France
facility: Centre Hospitalier Annecy-Genevois - Site d'Annecy
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Tours
country: France
facility: CHU de Tours - Hôpital Bretonneau
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: The Lymphoma Academic Research Organisation
name: Hervé Ghesquières, MD
role: PRINCIPAL_INVESTIGATOR
References: