Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell
- Conditions
- LymphomaLarge B-CellDiffuse Large B-Cell
- Interventions
- Registration Number
- NCT02916316
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- 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%.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 127
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Chemo immunotherapy R-CHOP with doxorubicin 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.
- Primary Outcome Measures
Name Time Method Cardiotoxicity 1 year from enrollment defined as the rate of cardiovascular events classified according to the Lenihan criteria 2013
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) 6 months from enrollment defined according to international criteria (Cheson 2007)
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.
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.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
Trial Locations
- Locations (18)
A.O. Universitaria Policlinico Di Modena
🇮🇹Modena, MO, Italy
UO Ematologia PO Vito Fazzi
🇮🇹Lecce, Italy
Nuovo Ospedale Di Sassuolo S.P.A.
🇮🇹Sassuolo, Modena, Italy
Ematologia e Trapianto Istituto Regina Elena IFO
🇮🇹Roma, Italy
UO Ematologia e CTMO di Piacenza
🇮🇹Piacenza, PC, Italy
Ospedale S. Giacomo di Castelfranco Veneto
🇮🇹Castelfranco Veneto, Italy
Ospedali Riuniti Villa Sofia - Cervello
🇮🇹Palermo, PA, Italy
AO Riuniti Papardo Piemonte
🇮🇹Messina, ME, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, MI, Italy
Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, MI, Italy
AOU Universitа degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Italy
U.O. Complessa di Ematologia Ospedale di Parma
🇮🇹Parma, Italy
Ospedale Ca Foncello
🇮🇹Treviso, Italy
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
🇮🇹Ancona, Italy
Ospedale Riuniti di Foggia
🇮🇹Foggia, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Osp.Sant'Eugenio Divisione di Ematologia
🇮🇹Roma, Italy