Clinical trial NCT02916316: Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell
Official title: Prospective Observational Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Lymphoma
Large B-Cell
Diffuse Large B-Cell
Keywords: Lymphoma
Large B-Cell
Cardiotoxicity
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2016-09-27
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Diffuse Large B-Cell Lymphoma

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%.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiotoxicity
timeFrame: 1 year from enrollment
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 6 months from enrollment
measure: Rate of response to treatment
timeFrame: 6 months from enrollment
measure: Overall survival (OS)
timeFrame: 3 years from enrollment
measure: Progression-free survival (PFS)
timeFrame: 3 years from enrollment
measure: failure-free survival (FFS)
timeFrame: 3 years from enrollment
measure: Freedom From cardiovascular Event (FFCE)
timeFrame: 3 years from enrollment
measure: Number of events recorded during the treatment and codified according to NCI-CTC v4.03
timeFrame: 3 years from enrollment
Other outcomes:
Locations:
city: Messina
country: Italy
facility: AO Riuniti Papardo Piemonte
state: ME
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: MI
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Sassuolo
country: Italy
facility: Nuovo Ospedale Di Sassuolo S.P.A.
state: Modena
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena
state: MO
city: Palermo
country: Italy
facility: Ospedali Riuniti Villa Sofia - Cervello
state: PA
city: Piacenza
country: Italy
facility: UO Ematologia e CTMO di Piacenza
state: PC
city: Ancona
country: Italy
facility: A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona
city: Castelfranco Veneto
country: Italy
facility: Ospedale S. Giacomo di Castelfranco Veneto
city: Foggia
country: Italy
facility: Ospedale Riuniti di Foggia
city: Lecce
country: Italy
facility: UO Ematologia PO Vito Fazzi
city: Napoli
country: Italy
facility: AOU Universitа degli Studi della Campania Luigi Vanvitelli
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Parma
country: Italy
facility: U.O. Complessa di Ematologia Ospedale di Parma
city: Reggio Emilia
country: Italy
facility: Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Ematologia e Trapianto Istituto Regina Elena IFO
city: Roma
country: Italy
facility: Osp.Sant'Eugenio Divisione di Ematologia
city: Treviso
country: Italy
facility: Ospedale Ca Foncello
Study officials:
affiliation: AOU Ospedali Riuniti, Ematologia ANCONA
name: Guido Gini, MD
role: PRINCIPAL_INVESTIGATOR
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