Diffuse Large B-Cell, Large B-Cell, Lymphoma
Conditions
Keywords
Lymphoma, Large B-Cell, Cardiotoxicity
Brief summary
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
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%.
Interventions
DRUGR-CHOP with doxorubicin
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.
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiotoxicity | 1 year from enrollment | defined as the rate of cardiovascular events classified according to the Lenihan criteria 2013 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of response to treatment | 6 months from enrollment | defined according to international criteria (Cheson 2007) |
| Overall survival (OS) | 3 years from enrollment | 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. |
| Progression-free survival (PFS) | 3 years from enrollment | It will be calculated for all patients from the start of therapy given to the date of progression or death or last follow-up. |
| Overall response rate (ORR) | 6 months from enrollment | defined according to international criteria (Cheson 2007) |
| Freedom From cardiovascular Event (FFCE) | 3 years from enrollment | 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. |
| Number of events recorded during the treatment and codified according to NCI-CTC v4.03 | 3 years from enrollment | it will be defined by the number of events recorded during the treatment and codified according to NCI-CTC v4.03 |
| failure-free survival (FFS) | 3 years from enrollment | 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. |
Countries
Italy
Outcome results
None listed