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

Sponsor

The Lymphoma Academic Research Organisation (Other)

Overall Status

Completed

CT.gov ID

NCT02414568

Collaborator

(none)

Enrollment

Locations

Arm

63.8

Actual Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma	Drug: Bendamustine Drug: Prednisone Drug: Vinblastine Drug: Doxorubicin	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

Open label

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 17, 2015

Actual Primary Completion Date :

Dec 14, 2018

Actual Study Completion Date :

Nov 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PVAB regimen 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 Bendamustine 120 mg/m2 (IV) Day 1 Other Names: LEVACT Drug: Prednisone Prednisone 40 mg/m² PO Other Names: CORTANCYL Drug: Vinblastine Vinblastine 6 mg/m² IV Other Names: VELBE Drug: Doxorubicin Doxorubicin 40 mg/m² IV Other Names: ADRIBLASTINE

Arm

Intervention/Treatment

Experimental: PVAB regimen

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

Bendamustine 120 mg/m2 (IV) Day 1

Other Names:

LEVACT

Drug: Prednisone

Prednisone 40 mg/m² PO

Other Names:

CORTANCYL

Drug: Vinblastine

Vinblastine 6 mg/m² IV

Other Names:

VELBE

Drug: Doxorubicin

Doxorubicin 40 mg/m² IV

Other Names:

ADRIBLASTINE

Outcome Measures

Primary Outcome Measures

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]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	A. Z. Sint-Jan	Bruges	Belgium	8000
2	Clinique Universitaire St Luc	Bruxelles	Belgium	1200
3	CHU de Liège	Liège	Belgium	4000
4	UCL Mont Godinne	Yvoir	Belgium	5530
5	CHU d'Amiens - Groupe Hospitalier Sud	Amiens	France	80054
6	Hôpital Jean Minjoz	Besancon	France	25030
7	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33300
8	CHRU de Brest - Hôpital Morvan	Brest	France	29609
9	CHU de Caen	Caen	France	14000
10	Médipôle de Savoie	Challes les eaux	France	73190
11	CH Sud Francilien	Corbeil Essonnes	France	91106
12	Hôpital Henri Mondor	Créteil	France	94010
13	CHU Dijon - Hôpital d'Enfants	Dijon	France	21000
14	CHU de Grenoble - Hôpital Albert Michallon	Grenoble	France	38043
15	CH Départemental Vendée	La Roche sur Yon	France	85925
16	CH de Versailles	Le Chesnay	France	78157
17	CH du Mans	Le Mans	France	72000
18	CHRU de Lille	Lille	France	59037
19	CHU de Limoges	Limoges	France	87042
20	Centre Léon Bérard	Lyon	France	69373
21	CHR de Metz-Thionville - Hôpital de Mercy	Metz	France	57085
22	Hôpital Lapeyronie	Montpellier	France	34295
23	CH de Mulhouse	Mulhouse	France	68070
24	CHU de Nantes - Hôtel Dieu	Nantes	France	44093
25	CHRU de Nîmes	Nîmes	France	30029
26	Hôpital de la Pitié-Salpêtrière	Paris	France	75013
27	Hôpital Saint Louis	Paris	France	75475
28	Hôpital Necker	Paris	France	75743
29	CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie	Pessac	France	33604
30	CHU Lyon Sud	Pierre-Bénite	France	69310
31	CHU Poitiers	Poitiers	France	86000
32	CH Rene Dubos	Pontoise	France	95303
33	Centre Hospitalier Annecy-Genevois - Site d'Annecy	Pringy	France	74374
34	CHU de Reims	Reims	France	51092
35	Hôpital Pontchaillou	Rennes	France	35033
36	Centre Henri Becquerel	Rouen	France	76038
37	CHU de Strasbourg	Strasbourg	France	67098
38	CHU de Tours - Hôpital Bretonneau	Tours	France	37044
39	CH de Valenciennes	Valenciennes	France	59322
40	CHU Brabois	Vandoeuvre les Nancy	France	54511