Dose-dense ABVD First Line Therapy in Early Stage Unfavorable Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Prospective, multicenter, Phase II trial designed to assess whether intensification of ABVD (dd-ABVD) is feasible and can improve the outcome of patients with early stage Hodgkin Lymphoma.

Detailed Description
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Dose-density has been shown to be an important factor for complete remission rate and longterm survival in lymphomas. The aims of this study were to find out whether intensification of ABVD (dd-ABVD) is feasible and can improve the outcome of patients with early stage Hodgkin Lymphoma. In view of emerging data on the role of early PET in defining prognosis in Hodgkin Lymphoma patients, the percentage of FDG-PET (fluorodeoxyglucose positron emission tomography) negativity after two cycle was chosen as the parameter to evaluate dd-ABVD activity.

Official Title
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Dose-dense ABVD as First Line Therapy in Early Stage Unfavorable Hodgkin's Lymphoma: a Phase II, Prospective, Multi-center Study

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: dose dense ABVD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years Histologically confirmed Hodgkin Lymphoma stage I, II unfavorable according to EORTC (European Organisation for Research and Treatment of Cancer) criteria, with exclusion of stage II B bulky. Previously untreated ECOG (Eastern Cooperative Oncology Group) performance status 0 - 2 Staging with FDG-PET (fluorodeoxyglucose positron emission tomography) Written informed consent Adequate liver and renal function (total serum bilirubin < 2.5 x ULN, AST/SGOT and/or ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement, serum creatinine < 2.5 x ULN) Exclusion Criteria: Concomitant cardiac, pulmonary, neurologic, psychiatric or metabolic severe disease. Uncontrolled diabetes mellitus (with fasting glucose levels above 200mg/dl) Other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast or other cancer from which the patient has been disease-free for ≥ 3 years Patients with a known history of HIV seropositivity Active HCV infection (PCR + ; AST> 1.5-2x UN) Woman who is pregnant or breast feeding. Fertile patients not willing to use effective contraception during the study and 3 months after the end of treatment. Women of childbearing potential (WOCBP) are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months. Negative pregnancy test at baseline is required (serum β HCG). Male patient whose sexual partner(s) are WOCBP who are not willing to use a effective contraception during the study and 3 months after the end of treatment Nodular lymphocyte prevalence histological subtype

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: dose dense ABVD<br>1 arm for all patients (dose dense ABVD on day 1 and 8 every 21 days) | Drug: dose dense ABVD<br>* dose dense ABVD will be administered intravenously on day 1 and 8 every 21 days Chemotherapy regimen Doxorubicin 25 mg/m2 i.v. day 1 and 8 Bleomycin 10 mg/m2 i.v. day 1 and 8 Vinblastine 6 mg/m2 i.v. day 1 and 8 Dacarbazine 375 mg/m2 i.v. day 1 and 8 Granulocyte colony-stimulating factor (G-CSF): days 9 to 14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility | Proportion of patient with a dose intensity reduction (lower than 85% of planned dose) | After 4 dd-ABVD cycles (12 weeks after starting treatment) | 
| Activity | Percentage of FDG PET negativity after 2 dd-ABVD cycles will be considered as primary endpoints. | After 2 dd-ABVD cycles (6 week after starting treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall accuracy of each interim PET interpretation criteria after a minimum follow-up of three years | Concordance between pet results and patients prognosis | After 3 years of follow-up | 
| PFS | Progression free survival estimate (prognosis outcome) | 2 years from the activation of therapy in the last patient enrolled onto the study. | 
| OS | Overall survival estimate (prognosis outcome) | 2 years from the activation of therapy in the last patient enrolled onto the study. | 
| Toxicity | Proportion of early and late toxicities (G3/4 acute toxicities, secondary malignancies, cardiovascular and pulmonary events, infertility) | 2 years from the activation of therapy in the last patient enrolled onto the study. | 
| Predictive Value of each interim PET interpretation criteria after a minimum follow-up of three years | Concordance between pet results and patients prognosis | After 3 years of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HL, Hodgkin Lymphoma, First line therapy