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

Classical Hodgkin Lymphoma Clinical Trial

— PVAB  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02414568
• Other study ID #: PVAB
• Status: Completed
• Phase: Phase 2
• Start date: July 17, 2015
• Est. completion date: November 10, 2020

Study information

• Verified date: February 2021
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: November 10, 2020
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• Bendamustine
Bendamustine 120 mg/m2 (IV) Day 1
• Prednisone
Prednisone 40 mg/m² PO
• Vinblastine
Vinblastine 6 mg/m² IV
• Doxorubicin
Doxorubicin 40 mg/m² IV

Locations

Country	Name	City	State
Belgium	A. Z. Sint-Jan	Bruges
Belgium	Clinique Universitaire St Luc	Bruxelles
Belgium	CHU de Liège	Liège
Belgium	UCL Mont Godinne	Yvoir
France	CHU d'Amiens - Groupe Hospitalier Sud	Amiens
France	Hôpital Jean Minjoz	Besancon
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	CHRU de Brest - Hôpital Morvan	Brest
France	CHU de Caen	Caen
France	Médipôle de Savoie	Challes les eaux
France	CH Sud Francilien	Corbeil Essonnes
France	Hôpital Henri Mondor	Créteil
France	CHU Dijon - Hôpital d'Enfants	Dijon
France	CHU de Grenoble - Hôpital Albert Michallon	Grenoble
France	CH Départemental Vendée	La Roche sur Yon
France	CH de Versailles	Le Chesnay
France	CH du Mans	Le Mans
France	CHRU de Lille	Lille
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	CHR de Metz-Thionville - Hôpital de Mercy	Metz
France	Hôpital Lapeyronie	Montpellier
France	CH de Mulhouse	Mulhouse
France	CHU de Nantes - Hôtel Dieu	Nantes
France	CHRU de Nîmes	Nîmes
France	Hôpital de la Pitié-Salpêtrière	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint Louis	Paris
France	CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie	Pessac
France	CHU Lyon Sud	Pierre-Bénite
France	CHU Poitiers	Poitiers
France	CH Rene Dubos	Pontoise
France	Centre Hospitalier Annecy-Genevois - Site d'Annecy	Pringy
France	CHU de Reims	Reims
France	Hôpital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	CHU de Strasbourg	Strasbourg
France	CHU de Tours - Hôpital Bretonneau	Tours
France	CH de Valenciennes	Valenciennes
France	CHU Brabois	Vandoeuvre les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Safety profile including immediate toxicities and non-tumor events	Safety profile including immediate toxicities and non-tumor events	5 years
Secondary	Progression-free survival	Progression-free survival	5 years
Secondary	Disease-free survival	Disease-free survival	5 years
Secondary	Overall survival	Overall survival	5 years
Secondary	Geriatric assessment program	7 Quality of Life Questionnaires (QLQ)	5 years