Clinical trial NCT01523847: A Multi-centre Study of MBVD in Elderly and/or Cardiopathic Patients Affected by Hodgkin's Lymphoma (HL)
Official title: A Phase II Multi-centre Study of MBVD in Elderly and/or Cardiopathic Patients Affected by Hodgkin's Lymphoma (HL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: Hodgkin Lymphoma
Cardiopathic
elderly
Myocet
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
First posted: 2012-02-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study has the purpose to evaluate in elderly and/or cardiopathic HL patients, the cardiologic toxicity of the MBVD regimen, where liposomal doxorubicin (Myocet®) is substituted for doxorubicin in the conventional ABVD regimen.

Detailed description: STUDY POPULATION Patients affected by Hodgkin's lymphoma, any stage, older than 69 years. Patients affected by Hodgkin's Lymphoma with concomitant cardiopaty, older than 18 years.

AIMS OF THE STUDY

* To evaluate in elderly and/or cardiopathic HL patients, the cardiologic toxicity of the MBVD regimen, where liposomal doxorubicin (Myocet®) is substituted for doxorubicin in the conventional ABVD regimen
* To compare in a pair-match retrospective analysis the results obtained with MBVD with those obtained in patients comparable for clinical variables and treated with ABVD or with the reduced intensity VEPEMB schedule.

STUDY DESIGN Multi-centre phase II study SAMPLE SIZE 50 patients

STUDY PROCEDURES

* Histologic diagnosis of Hodgkin Lymphoma.
* Early Staging evaluation including:

  * Blood tests
  * CT, PET and bone marrow biopsy.
  * Heart and lung function evaluation.
  * Geriatric assessment.
  * Quality of life evaluation.
* 2 MBVD courses
* Early restaging with PET scan (PET-2)
* The subsequent treatment will be planned as follows:

  * Stage I and IIA patients will go on with 1 more course of MBVD (total of 3 courses) followed by involved field radiotherapy (30 Gy-36Gy).
  * Advanced stage (IIB-IV) patients will go on with 4 more courses of MBVD (total of 6 courses). Radiotherapy limited to bulky or non complete responder areas (30-36 Gy) is optional.
* Final restaging including:

  * Blood tests
  * CT, PET
  * bone marrow biopsy if positive at baseline.
  * Heart and lung function evaluation.
  * Geriatric assessment.
  * Quality of life evaluation

Follow up procedures will include:

1. a clinical and laboratory evaluation (with troponin, proBNP / BNP, cardiology visit, ECG and echocardiogram) every 6 months in the first 2 years, then annually.
2. CT scans will be planned annually.
3. Compilation of geriatric evaluation scales every 6 months in the first 2 years, then annually.

MBVD will be scheduled as follows (4 weeks):

Myocet 25 mg/mq i.v. day 1 and 15 Bleomycin 10 mg/mq i.v. day 1 and 15 Vinblastine 6 mg/mq i.v. day 1 and 15 Dacarbazine 375 mg/mq i.v. day 1 and 15 Supportive treatment with G-CSF and/or Erythropoietin will be planned according to international guide-lines.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed Hodgkin's lymphoma, except for nodular lymphocyte predominance subgroup.
* Previously untreated
* Age ≥ 70.
* Age\> 18 in presence of cardiopathy according to inclusion criteria...
* Patients with HCV and HBV infection can be included. For patients HBV+ occult carriers (AntiHBc+, HbsAg-, AntiHBs+/-) Lamivudine prophylaxis is mandatory.
* Life expectancy \>3 months
* Informed consent.
* Staging with PET-CT.
* Preliminary geriatric assessment (ADL, IADL, co-morbidity and frailness scores).

Exclusion Criteria:

* Lymphocyte predominance subgroup
* Age \< 70 (no cardiopathy)
* Age \< 18 (with cardiopathy).
* HIV infection.
* Previous treatments for Hodgkin's lymphoma.
* Other concomitant or previous malignancies, with the exception of basal cell skin tumors, adequately treated carcinoma in situ of the cervix and any cancer that has been in complete remission for \> 5 years.
* Renal failure (creatinine higher than twice the normal level) or liver disease (AST/ALT or bilirubin level higher than 2.5 times the normal level)
* Other clinical situations that contraindicate, to the judgment of investigators, the administration of a mild-dose chemotherapy. Isolated comorbidities will be scored and recorded, but they are not, if isolated, a sufficient reason for exclusion.
* Frail patients, defined according to comorbidity scale: patients with 1 grade 4 comorbidity, or \>3 grade 3 comorbidities, are excluded. (see appendix.6)
* Unresponsive sepsis
* Dementia
* Impossibility to subscribe the informed consent

Primary outcomes:
measure: Complete Response (CR) at the end of the chemotherapy program
timeFrame: 24 weeks
measure: Cardiac Toxicity during the chemotherapy program measured by CTCAE v.3
timeFrame: 24 weeks
Secondary outcomes:
measure: Cardiac toxicity of MBVD after two courses of MBVD measured by CTCAE v.3
timeFrame: 8 weeks
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Relapse Free Survival (RFS) of patients entering complete remission
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Change from the theoretical total amount of drug delivered in a one-week period (dose-intensity)
timeFrame: 24 weeks
measure: Change in cardiac markers during and at the end of chemotherapy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Tricase
country: Italy
facility: Ospedale Cardinale Giovanni Panico
state: Lecce
city: Civitanova Marche
country: Italy
facility: A.S.U.R. Zona Territoriale n°8 - Ospedale di Civitanova Marche U.O. Medicina Interna ed Ematologia
state: Macerata
city: Ivrea
country: Italy
facility: SC Medicina trasfusionale ed Ematologia Ospedale civile di Ivrea
state: Torino
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo
city: Aviano
country: Italy
facility: Centro di riferimento Oncologico
city: Bari
country: Italy
facility: IRCC Istituto Tumori
city: Bologna
country: Italy
facility: Policlinico S. Orsola Malpighi
city: Brescia
country: Italy
facility: Spedali Civili
city: Brindisi
country: Italy
facility: Ospedale "A. Perrino"
city: Cagliari
country: Italy
facility: Ospedale Businco
city: Lecce
country: Italy
facility: Ematologia Ospedale Vito Fazzi
city: Meldola (FC)
country: Italy
facility: Area Vasta Romagna e IRST
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Palermo
country: Italy
facility: Azienda Ospedaliera V.Cervello
city: Pavia
country: Italy
facility: Fondazione Policlinico San Matteo
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto
city: Ravenna
country: Italy
facility: Osp. S. Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera "Bianchi Melacrino Morelli"
city: Reggio Emilia
country: Italy
facility: Ematologia Azienda Ospedaliera Arcispedale "S. Maria Nuova"
city: Rimini
country: Italy
facility: Divisione di Oncologia Ospedale civile degli Infermi
city: Roma
country: Italy
facility: U.O.C. Ematologia IRCCS Istituti Fisioterapici Ospitalieri
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Roma
country: Italy
facility: Università "La Sapienza"
city: Terni
country: Italy
facility: Ospedale Santa Maria
city: Treviso
country: Italy
facility: Struttura Complessa di Ematologia PO TREVISO
city: Udine
country: Italy
facility: Azienda Ospedaliero - Universitaria di Udine
Study officials:
affiliation: Azienda Ospedaliera SS Antonio, Biagio e Cesare Arrigo
name: Alessandro Levis, PhD
role: STUDY_DIRECTOR
References: