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

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

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.

Study Overview

• Status: Completed
• Conditions: Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Bendamustine; Drug: Prednisone; Drug: Vinblastine; Drug: Doxorubicin

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruges, Belgium, 8000
    • A. Z. Sint-Jan
  • Bruxelles, Belgium, 1200
    • Clinique Universitaire St LUC
  • Liège, Belgium, 4000
    • CHU de Liège
  • Yvoir, Belgium, 5530
    • UCL Mont Godinne
• France
  • Amiens, France, 80054
    • CHU d'Amiens - Groupe Hospitalier Sud
  • Besancon, France, 25030
    • Hôpital Jean Minjoz
  • Bordeaux, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Brest, France, 29609
    • CHRU de Brest - Hôpital Morvan
  • Caen, France, 14000
    • CHU de Caen
  • Challes les eaux, France, 73190
    • Médipôle de Savoie
  • Corbeil Essonnes, France, 91106
    • CH Sud Francilien
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Dijon, France, 21000
    • CHU Dijon - Hôpital d'Enfants
  • Grenoble, France, 38043
    • CHU de Grenoble - Hôpital Albert Michallon
  • La Roche sur Yon, France, 85925
    • CH Départemental Vendée
  • Le Chesnay, France, 78157
    • CH de Versailles
  • Le Mans, France, 72000
    • CH du Mans
  • Lille, France, 59037
    • CHRU de Lille
  • Limoges, France, 87042
    • Chu de Limoges
  • Lyon, France, 69373
    • Centre Leon Berard
  • Metz, France, 57085
    • CHR de Metz-Thionville - Hôpital de Mercy
  • Montpellier, France, 34295
    • Hopital Lapeyronie
  • Mulhouse, France, 68070
    • CH de Mulhouse
  • Nantes, France, 44093
    • CHU de Nantes - Hotel Dieu
  • Nîmes, France, 30029
    • CHRU de Nîmes
  • Paris, France, 75475
    • Hôpital Saint Louis
  • Paris, France, 75743
    • Hôpital Necker
  • Paris, France, 75013
    • Hôpital de la Pitié-Salpétrière
  • Pessac, France, 33604
    • CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
  • Pierre-Bénite, France, 69310
    • CHU Lyon Sud
  • Poitiers, France, 86000
    • CHU Poitiers
  • Pontoise, France, 95303
    • CH René Dubos
  • Pringy, France, 74374
    • Centre Hospitalier Annecy-Genevois - Site d'Annecy
  • Reims, France, 51092
    • CHU de Reims
  • Rennes, France, 35033
    • Hopital Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Strasbourg, France, 67098
    • CHU de Strasbourg
  • Tours, France, 37044
    • CHU de Tours - Hôpital Bretonneau
  • Valenciennes, France, 59322
    • CH de Valenciennes
  • Vandoeuvre les Nancy, France, 54511
    • CHU Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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
Overall survival	Overall survival	5 years
Disease-free survival	Disease-free survival	5 years
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
Geriatric assessment program	7 Quality of Life Questionnaires (QLQ)	5 years

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Investigators: Principal Investigator: Hervé Ghesquières, MD, The Lymphoma Academic Research Organisation

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2015
• Primary Completion (Actual): December 14, 2018
• Study Completion (Actual): November 10, 2020

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Bendamustine Hydrochloride; Prednisone; Doxorubicin; Vinblastine
• Other Study ID Numbers: PVAB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No