Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Follicular

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Follicular Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

R-COMP Regimen:

Day 1: Rituximab 375 mg/m2; Myocet® 50 mg/m2; cyclophosphamide 750 mg/m2; vincristine 1.4 mg/m2 (maximum 2 mg); prednisone 60 mg/m2 Days 2-5: Prednisone, 60 mg/m2 Administered every 21 days × 6 cycles

R-CHOP Regimen:

Day 1: Rituximab 375 mg/m2; Doxorubicin 50 mg/m2; cyclophosphamide 750 mg/m2; vincristine 1.4 mg/m2 (maximum 2 mg); prednisone 60 mg/m2 Days 2-5: Prednisone, 60 mg/m2 Administered every 21 days × 6 cycles

Day 1: Rituximab 375 mg/m2; Myocet® 50 mg/m2; cyclophosphamide 750 mg/m2; vincristine 1.4 mg/m2 (maximum 2 mg); prednisone 60 mg/m2 Days 2-5: Prednisone, 60 mg/m2 Administered every 21 days × 6 cycles

RCOMP

Day 1: Rituximab 375 mg/m2; Doxorubicin 50 mg/m2; cyclophosphamide 750 mg/m2; vincristine 1.4 mg/m2 (maximum 2 mg); prednisone 60 mg/m2 Days 2-5: Prednisone, 60 mg/m2 Administered every 21 days × 6 cycles

RCHOP

Dr. Alejandro Martin

Dr. Juan Manuel Sancho

Dr. Francisco Gual

The Phase II study proposed here assesses the hypothesis that replacing doxorubicin by Myocet® in the R-CHOP regimen would yield comparable antitumour efficacy with a lower cardiotoxicity for first-line treatment in elderly patients with non-localised DLBCL/Follicular lymphoma grade IIIb

Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin's lymphoma (NHL). This is an aggressive lymphoma, with an incidence in Western countries estimated at 5-6 cases/100,000 inhabitants/year that increases with age.

Treatment for patients with DLBCL is currently based on immunochemotherapy, of which the R-CHOP regimen, which includes cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in combination with the anti-CD20 monoclonal antibody rituximab and is administered every 21 days for a total of 6-8 cycles, is the most commonly used.

Cardiotoxicity is one of the undesirable effects that limit the use of anthracyclines, such as doxorubicin, as part of the CHOP regimen, which is caused by the formation of complexes between ferric ions and the anthracycline within the myocyte. Because of their oxidative properties, these complexes are toxic and produce highly reactive free radicals that damage the lipid membrane and lead to the cell death of myocytes. Several studies have linked the onset of cardiotoxicity with old age, high cumulative doses of doxorubicin, cardiovascular risk factors and previous heart disease, among others. Anthracycline-induced cardiotoxicity is cumulative and irreversible. Moreover, left ventricular dysfunction is an important late effect in patients with aggressive NHL who survive long term and, according to some studies, have received doxorubicin at doses higher than 200 mg/m². Cardiotoxicity may be silent or subclinical, which is usually detected as a decrease in left ventricular ejection fraction (LVEF), or clinical, with varying degrees of congestive heart failure (CHF). Depending on the symptoms, cardiotoxicity also differs between acute, subacute, late or chronic. The first is manifested at an early stage, usually as arrhythmia, transient ECG changes or pericarditis, among others, is usually reversible, is not detrimental to the continuation of treatment and is not associated with subacute and late toxicity.

Chronic cardiotoxicity could be early or late. Early-onset cardiotoxicity occurs within 1 year after anthracycline treatment and late-onset cardiotoxicity occurs more than 1 year after completion of anthracycline treatment. In the latter two, cardiotoxicity is associated with the lesion of cardiomyocytes and is therefore considered irreversible. The incidence of cardiotoxicity varies among different studies, depending on patient follow-up or the definition of cardiotoxicity used (acute, subacute or late).

In addition to clinical findings, the determination of LVEF or, more recently, the use of biomarkers, are the most commonly used methods to diagnose and assess cardiotoxicity. Regarding the identification of biomarkers, troponin I and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) are the most commonly used and investigated in the context of clinical studies. The advantages of using biomarkers include their minimally invasive identification, which is less expensive than echocardiography, and, unlike radionuclide ventriculography, they avoid irradiation of the patient. Furthermore, the interpretation of their results does not depend on the observer's experience, thus avoiding interobserver variability. Several studies have shown the role of troponins as indicators of early anthracycline-induced cardiotoxicity or other chemotherapeutic agents, which are able to predict impaired ventricular function and higher incidence of cardiac events in patients with elevated values of this marker compared with patients with normal troponin values. Regarding the use of brain natriuretic peptides such as NT-proBNP, several studies have shown a correlation between persistently high values of this biomarker and impaired heart function parameters, in particular LVEF.

Myocet® (non-pegylated liposomal doxorubicin) is one of the several strategies developed to reduce cardiotoxicity and maintain the therapeutic efficacy of the R-CHOP regimen. Non-pegylated liposomal doxorubicin has shown a similar efficacy and less cardiotoxicity than conventional doxorubicin in the treatment of women with metastatic breast cancer. In addition, several studies in patients with NHL have shown similar response rates with regimens containing non-pegylated liposomal doxorubicin to those obtained in historical controls with conventional doxorubicin, with a low incidence of clinical and subclinical cardiovascular events. The treatment is relatively well tolerated, while myelosuppression is its most important toxicity.

Most of these phase I and II studies (with or without rituximab), which assessed Myocet® in combination with cyclophosphamide; vincristine and prednisone, showed that it is an active treatment in newly diagnosed patients with aggressive NHL.

100% of the data registered on CRFs will be source data verified. eCRDs will be used in order to register the data. Nine monitoring visits per site will be performed.

First monitoring vistit will be performed when the first patient is included Second monitoring visit willb be performed when the third patient is included Third monitoring visit will be perforemd when the fifth patient is included Fourth monitoring visit will be performed then the last patient finish study treatment One monitoring visit per year will be performed during follow-up phase.

CRO (Dynamic) Standard Operating Procedures will be used to manage the clinical trial.

Sample size of the study is based on the hypothesis of a LEVF decrease \<55% in the 15% of patients assigned to R-CHOP treatment group and 5% of patients assigned to R-COMP treatment group.

Categorical variables were show by absolute and relative frequencies, including the confidence interval of 95%.

For the description of the continuous variables will be use the mean, standard deviation, median, mode, minimum and maximum, including the total number of valid values.

In the case of compare subgroups of patients, will be use for quantitative variables parametric tests or nonparametric as characteristics of the variables under study. For qualitative variables will be use Chi-square test.

Statistical analysis was planned with the SAS statistical package version 9.1 or later.

Two interim analysis will be performed when the last patient peforms the end of treatment visit and when the last patient performd the 24 months follow-up visit.

Final analysis will be performed at the end of the study.

Clinical Trial to Evaluate R-COMP Versus R-CHOP in Newly Diagnosed Patients With Non-localised Diffuse Large B-cell Lymphoma (DLBCL)/Follicular Lymphoma Grade IIIb

Phase II, Randomised, Multicentre Study With Two Treatment Arms (R-COMP Versus R-CHOP) in Newly Diagnosed Elderly Patients (≥60 Years) With Non-localised Diffuse Large B-cell Lymphoma (DLBCL)/Follicular Lymphoma Grade IIIb.

Subclinical cardiac toxicity determined by the percentage of measurings experiencing a decrease in LEVF determined by echocardiography with final LEVF \<55% at day 135

Subclinical cardiac toxicity determined by the percentage of measurings experiencing a decrease in LEVF determined by echocardiography with final LEVF \<55% at day 225

Event free survial, progression free survival and overall survival at 2 and 5 years.

Overall response rates and complete responses evaluated by the International Harmonization Project for response criteria in lymphoma

Rate of cardiac/cardiovascular toxicity according to the CTC criteria (version 4.0) of the National Cancer Institute (NCI) during the treatment and during 5 years

No cardiotoxicity according to the CTC criteria (version 4.0) of the NCI during 24 months

Cardiotoxicity determined by elevated values of troponin and NT-proBNP and decreased values of LEVF determined during 12 months

Spots Global Cancer Trial Database for rcomp

Every month we try and update this database with for rcomp cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for rcomp

Every month we try and update this database with for rcomp cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for rcomp cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.