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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02916316
• Other study ID #: FIL_Cardio-DLBCL
• Status: Active, not recruiting
• Start date: February 12, 2014
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: Fondazione Italiana Linfomi - ETS
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 127
• Est. completion date: December 2024
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Cardiotoxicity
• Diffuse Large B-Cell
• Large B-Cell
• Lymphoma

Intervention

Drug:
• R-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.

Locations

Country	Name	City	State
Italy	A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona	Ancona
Italy	Ospedale S. Giacomo di Castelfranco Veneto	Castelfranco Veneto
Italy	Ospedale Riuniti di Foggia	Foggia
Italy	UO Ematologia PO Vito Fazzi	Lecce
Italy	AO Riuniti Papardo Piemonte	Messina	ME
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	MI
Italy	A.O. Universitaria Policlinico Di Modena	Modena	MO
Italy	AOU Universit? degli Studi della Campania Luigi Vanvitelli	Napoli
Italy	Istituto Oncologico Veneto	Padova
Italy	Ospedali Riuniti Villa Sofia - Cervello	Palermo	PA
Italy	U.O. Complessa di Ematologia Ospedale di Parma	Parma
Italy	UO Ematologia e CTMO di Piacenza	Piacenza	PC
Italy	Azienda Unit? Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Ematologia e Trapianto Istituto Regina Elena IFO	Roma
Italy	Osp.Sant'Eugenio Divisione di Ematologia	Roma
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Nuovo Ospedale Di Sassuolo S.P.A.	Sassuolo	Modena
Italy	Ospedale Ca Foncello	Treviso

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi - ETS

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Balzarotti M, Spina M, Sarina B, Magagnoli M, Castagna L, Milan I, Ripa C, Latteri F, Bernardi D, Bertuzzi A, Nozza A, Roncalli M, Morenghi E, Tirelli U, Santoro A. Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide. Ann Oncol. 2002 Sep;13(9):1341-6. doi: 10.1093/annonc/mdf242. — View Citation

Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997 Jun;12(3):177-86. doi: 10.1089/cbr.1997.12.177. — View Citation

Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. doi: 10.1056/NEJM199304083281404. — View Citation

Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361-92. No abstract available. — View Citation

International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993 Sep 30;329(14):987-94. doi: 10.1056/NEJM199309303291402. — View Citation

Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. doi: 10.1182/blood-2003-06-2095. Epub 2004 Mar 11. — View Citation

Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rube C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. doi: 10.1182/blood-2003-06-2094. Epub 2004 Feb 24. — View Citation

Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. doi: 10.1182/blood-2003-02-0542. Epub 2003 Aug 14. — View Citation

Vitolo U, Liberati AM, Cabras MG, Federico M, Angelucci E, Baldini L, Boccomini C, Brugiatelli M, Calvi R, Ciccone G, Genua A, Deliliers GL, Levis A, Parvis G, Pavone E, Salvi F, Sborgia M, Gallo E; Intergruppo Italiano Linfomi. High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an "Intergruppo Italiano Linfomi" randomized trial. Haematologica. 2005 Jun;90(6):793-801. — View Citation

Wilson WH. Chemotherapy sensitization by rituximab: experimental and clinical evidence. Semin Oncol. 2000 Dec;27(6 Suppl 12):30-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiotoxicity	defined as the rate of cardiovascular events classified according to the Lenihan criteria 2013	1 year from enrollment
Secondary	Overall response rate (ORR)	defined according to international criteria (Cheson 2007)	6 months from enrollment
Secondary	Rate of response to treatment	defined according to international criteria (Cheson 2007)	6 months from enrollment
Secondary	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
Secondary	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
Secondary	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	3 years from enrollment
Secondary	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
Secondary	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