HD0803: A Multi-centre Study of MBVD in Elderly and/or Cardiopathic Patients Affected by Hodgkin's Lymphoma (HL)

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Completed

CT.gov ID

NCT01523847

Collaborator

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte (Other)

Enrollment

Locations

Arm

Duration (Months)

1.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma	Drug: MBVD (Myocet+BVD)	Phase 2

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:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Multi-centre Study of MBVD in Elderly and/or Cardiopathic Patients Affected by Hodgkin's Lymphoma (HL)

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MBVD (Myocet+BVD) 2 MBVD courses, after 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-36 Gy). -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 Gy) is optional.	Drug: MBVD (Myocet+BVD) MBVD will be scheduled as follows: 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 Other Names: MBVD

Arm

Intervention/Treatment

Experimental: MBVD (Myocet+BVD)

2 MBVD courses, after 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-36 Gy). -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 Gy) is optional.

Drug: MBVD (Myocet+BVD)

MBVD will be scheduled as follows: 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

Other Names:

MBVD

Outcome Measures

Primary Outcome Measures

Complete Response (CR) at the end of the chemotherapy program [24 weeks]
CR is defined according to the Cheson 2007 response criteria.
Cardiac Toxicity during the chemotherapy program measured by CTCAE v.3 [24 weeks]
Evaluation of Cardiac Toxicity during the chemotherapy program measured by CTCAE v.3

Secondary Outcome Measures

Cardiac toxicity of MBVD after two courses of MBVD measured by CTCAE v.3 [8 weeks]
Evaluation of cardiac toxicity of MBVD in elderly and/or cardiopathic patients with Hodgkin's lymphoma after two courses of MBVD.
Progression Free Survival (PFS) [24 months]
PFS will be measured from the day of enrolment to the date of disease progression, relapse or death due to any cause
Relapse Free Survival (RFS) of patients entering complete remission [24 months]
RFS is defined only for patients who achieve CR, and is measured from the date of attaining the disease-free state until the date of relapse or death from any cause
Overall Survival (OS) [24 months]
OS will be measured from the day of enrolment to the date of relapse or death due to any cause
Change from the theoretical total amount of drug delivered in a one-week period (dose-intensity) [24 weeks]
Proportion of dose-intensity delivered to patients
Change in cardiac markers during and at the end of chemotherapy [24 weeks]
Evaluate Change in cardiac markers during and at the end of chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ospedale Cardinale Giovanni Panico	Tricase	Lecce	Italy	73039
2	A.S.U.R. Zona Territoriale n°8 - Ospedale di Civitanova Marche U.O. Medicina Interna ed Ematologia	Civitanova Marche	Macerata	Italy	62012
3	SC Medicina trasfusionale ed Ematologia Ospedale civile di Ivrea	Ivrea	Torino	Italy	10015
4	Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo	Alessandria		Italy	15121
5	Centro di riferimento Oncologico	Aviano		Italy
6	IRCC Istituto Tumori	Bari		Italy
7	Policlinico S. Orsola Malpighi	Bologna		Italy
8	Spedali Civili	Brescia		Italy
9	Ospedale "A. Perrino"	Brindisi		Italy	72100
10	Ospedale Businco	Cagliari		Italy
11	Ematologia Ospedale Vito Fazzi	Lecce		Italy	73100
12	Area Vasta Romagna e IRST	Meldola (FC)		Italy
13	Ospedale Maggiore della Carità	Novara		Italy
14	Azienda Ospedaliera V.Cervello	Palermo		Italy	90146
15	Fondazione Policlinico San Matteo	Pavia		Italy
16	Ospedale Guglielmo da Saliceto	Piacenza		Italy	29100
17	Osp. S. Maria delle Croci	Ravenna		Italy
18	Azienda Ospedaliera "Bianchi Melacrino Morelli"	Reggio Calabria		Italy	89124
19	Ematologia Azienda Ospedaliera Arcispedale "S. Maria Nuova"	Reggio Emilia		Italy	42100
20	Divisione di Oncologia Ospedale civile degli Infermi	Rimini		Italy	47900
21	U.O.C. Ematologia IRCCS Istituti Fisioterapici Ospitalieri	Roma		Italy	00144
22	Ospedale S. Eugenio	Roma		Italy
23	Università "La Sapienza"	Roma		Italy
24	Ospedale Santa Maria	Terni		Italy
25	Struttura Complessa di Ematologia PO TREVISO	Treviso		Italy	31100
26	Azienda Ospedaliero - Universitaria di Udine	Udine		Italy