Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell

Study Overview
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Brief Summary
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All patients enrolled in the study will have to be treated with a chemo immunotherapy scheme R-CHOP with doxorubicin, with doxorubicin analogue or non pegylated liposomal anthracycline (R-COMP; Sec. 648 DM) administered every 21 days for 6 cycles. In unfavourable patients (stage II-IV) are allowed 2 additional cycles of rituximab at the end of the 6 cycles of R-CHOP.

Detailed Description
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The study was designed as a prospective observational multicenter study to evaluate the role of possible early markers of cardiotoxicity estimating an overall maximum risk equal to 20% of patients. The sample size, required to obtain an estimate of conventional anthracycline cardiotoxicity in the population, has been calculated with a confidence interval of 95% and a maximum acceptable error of ± 0.075. According to the conditions described above, the sample size of patients treated with conventional anthracycline results to be 124 patients. Considering a 10-15% of not evaluable patients, the sample size is fixed at 150 patients treated with R-CHOP. The duration of the enrollment phase is defined in 2 years. With this sample size should be possible to assess the risk of cardiotoxicity related to predictors with a worst group frequency at least of 10%.

Official Title
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Prospective Observational Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell

Conditions
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Large B-Cell, Lymphoma, Diffuse Large B-Cell

Intervention / Treatment
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* Drug: R-CHOP with doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Diffuse Large B-Cell Lymphoma diagnosis Patient eligible to receive 6 cycles of R-CHOP or R-CHOP like chemotherapy at full doses Age ≥ 18 Stage I-IV Written informed consent ECOG Performance Status 0-3 Ventricular Ejection Fraction (VEF) ≥40% No previous treatment for lymphoma (except for RT-IF) Negative β-HCG pregnancy test result at diagnosis for female of childbearing potential Use of acceptable method of contraception during the study and for 3 months after receiving the last dose of study drug for patients with childbearing potential Availability of the patient to be followed for all the phases of the chemotherapy treatment and for the subsequent follow-up Exclusion Criteria: Inability to schedule a treatment at full doses of chemoimmunotherapy R-CHOP or R-CHOP-like for different reasons Central nervous system involvement due to lymphoma HIV Active cardiac pathology including heart failure, left ventricular dysfunction documented by a LVEF <40%, arrhythmias (rapid atrial fibrillation, frequent ventricular arrhythmias), valvular aortic or mitral disfunction > moderate, ischemic heart disease (myocardial infarction or acute coronary syndrome for over 6 months, angina at rest or with mild efforts) Previous treatment for lymphoma Other malignancy in the 3 years prior to the diagnosis of lymphoma with exception of non-melanoma skin cancer or in situ carcinoma Any other co-existing medical condition that would preclude participation in the study (uncontrolled bacterial or viral or fungal infection) Pregnant, or lactating and breastfeeding female

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chemo immunotherapy<br>All patients enrolled in the study will have to be treated with a chemo immunotherapy scheme R-CHOP with doxorubicin, with doxorubicin analogue or non pegylated liposomal anthracycline (R-COMP; Sec. 648 DM) administered every 21 days for 6 cycles. In unfavourable patients (stage II-IV) are allowed 2 additional cycles of rituximab at the end of the 6 cycles of R-CHOP. | Drug: R-CHOP with doxorubicin<br>* Chemoimmunotherapy every 21 days for 6 cycles. In unfavourable patients (stage II-IV) are allowed 2 additional cycles of rituximab at the end of the 6 cycles of R-CHOP.<br>* Other names: R-COMP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiotoxicity | defined as the rate of cardiovascular events classified according to the Lenihan criteria 2013 | 1 year from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | defined according to international criteria (Cheson 2007) | 6 months from enrollment | 
| Rate of response to treatment | defined according to international criteria (Cheson 2007) | 6 months from enrollment | 
| Overall survival (OS) | It will be calculated for all patients enrolled in the study from the date of start of therapy to the date of death or last follow-up. | 3 years from enrollment | 
| Progression-free survival (PFS) | It will be calculated for all patients from the start of therapy given to the date of progression or death or last follow-up. | 3 years from enrollment | 
| failure-free survival (FFS) | It will be calculated for all patients from the therapy start date to the date of an event or last follow-up. The events considered for the FFS definition are the following: treatment discontinuation for toxicity, response <RC, relapse / progression, death for any cause. | 3 years from enrollment | 
| Freedom From cardiovascular Event (FFCE) | calculated for all patients from the therapy start date to the time of occurrence of a cardiovascular event as defined by primary endopoint or follow-up date. | 3 years from enrollment | 
| Number of events recorded during the treatment and codified according to NCI-CTC v4.03 | it will be defined by the number of events recorded during the treatment and codified according to NCI-CTC v4.03 | 3 years from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Large B-Cell, Cardiotoxicity