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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: MBVD (Myocet+BVD)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBVD (Myocet+BVD)<br>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)<br>* 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<br>* Other names: MBVD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) at the end of the chemotherapy program | CR is defined according to the Cheson 2007 response criteria. | 24 weeks | 
| Cardiac Toxicity during the chemotherapy program measured by CTCAE v.3 | Evaluation of Cardiac Toxicity during the chemotherapy program measured by CTCAE v.3 | 24 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin Lymphoma, Cardiopathic, elderly, Myocet