Emesis Control Study in Non-Hodgkin Lymphoma Patients Receiving R-CHOP

Study Overview
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Brief Summary
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The incidence and severity of chemotherapy-induced nausea and vomiting (CINV) in patients receiving R-CHOP chemotherapy for in non-Hodgkin's lymphoma is not well documented. The contribution of prednisolone to CINV control in the R-CHOP regimen is also unclear. This study aims to evaluate the overall effectiveness of antiemetic control using a standardised 5HT3 (5-Hydroxytryptamine 3) antagonist-containing regimen (e.g. ondansetron) in a heterogeneous group of patients receiving R-CHOP chemotherapy (Rituximab Doxorubicin Vincristine Cyclophosphamide Prednisolone).

Detailed Description
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The aim of this study will be to investigate the incidence and severity of CINV in patients receiving R-CHOP for the treatment of non-Hodgkin lymphoma and standardised antiemetic prophylaxis. The study hypothesises that the control of delayed nausea and emesis is suboptimal in a proportion of patients receiving R-CHOP regimens and that delayed CINV is not prevented by use of 5HT3 antagonists beyond the first day of use post-chemotherapy administration. Participating institutions will prospectively collect data on the incidence of CINV, the severity of CINV, the use of break through/rescue medication for episodes of CINV uncontrolled by prescribed regular antiemetics, the effectiveness of additional measures used when previous CINV control has been inadequate (for example the use of aprepitant as an additional measure in subsequent cycles) and the major side-effects likely to be related to the antiemetics. The analysis of these results will determine the incidence and severity of CINV in patients receiving R-CHOP and the effectiveness of the prescribed antiemetic regimens. Analysis will also determine if the control and incidence of CINV is a significant problem in defined subgroups of patients receiving R-CHOP and could inform the design of future research (or an extension of the current protocol) in this area. Sub groups for investigation will include patients with advanced disease, those with abdominal involvement, those receiving R-CHOP every 14 days versus every 21 days (R-CHOP14 versus R-CHOP21), those receiving 6 or 8 treatment cycles of R-CHOP, older patients, younger females etc. A potential randomised study evaluating the role of aprepitant could be contemplated in high risk groups.

Official Title
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A Single Arm Study to Evaluate the Control of Chemotherapy Induced Nausea and Vomiting in Non-Hodgkin Lymphoma Patients Receiving R-CHOP.

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Standard anti-emetics in conjunction with R-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of non Hodgkin's Lymphoma Newly diagnosed or relapsed patients who are chemotherapy-naïve or who have not received chemotherapy in the last 12 months. Pre-phase therapy with prednisolone and/or vincristine for < one week duration prior to commencement of cycle 1 of R-CHOP is permissible Intended to receive R-CHOP every 14 or 21 days for minimum 3 cycles with rituximab planned to be given with CHOP on day 1 or fractionated over days 1 and 21. Males and females, age 18 years or older Are reasonably expected to be able to complete the CINV tool Willing to complete assessments and tool as required for the study ECOG (Eastern Cooperative Oncology Group) performance status score of 2 or less Has provided written informed consent Exclusion Criteria: Women who are pregnant or lactating. Previous adverse reaction to the standard anti-emetics proposed in the study Contraindications to the use of the anti-emetics included as standard of care in the study (e.g. cardiac, liver function) Participation in other therapeutic studies investigating CINV. Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: R-CHOP and standard anti-emetics<br>This is a single arm study. All patients receive R-CHOP every 14 or 21 days for a minimum of 3 cycles. Standard anti-emetics will be used as follows: 5HT3 (5-Hydroxytryptamine 3) antagonists (ondansetron, granisetron or tropisetron) used as the local institutional standard of care will be permitted, although the preferential use of ondansetron or granisetron will be encouraged. Dexamethasone will not to be used as patients receive hydrocortisone and oral prednisolone in R-CHOP. In this study, the use of oral prednisolone on day 1 will be regarded as equivalent to dexamethasone. Prednisolone will be given PRIOR to the chemotherapy with the 5HT3 antagonist. Anti-emetics (metoclopramide, prochlorperazine and lorazepam) may be prescribed to be used 'as needed' for breakthrough emesis. Patients 'failing' the standard Chemotherapy Induced Nausea and Vomiting prophylactic regimen will be eligible to receive aprepitant (Days 1 to 3) for subsequent cycles. | Drug: Standard anti-emetics in conjunction with R-CHOP<br> <br> * Other names: aprepitant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response, Acute Phase (Day 1), Cycle 1 | The proportion of patients experiencing a complete response defined as no vomiting and no use of breakthrough medication in the acute phase (day 1: 0 - 24 hours) of the first cycle of R-CHOP chemotherapy | Day 1 | 
| Complete Response, Delayed Phase (Days 2 to 11), Cycle 1 | The proportion of patients experiencing a complete response defined as no vomiting and no use of breakthrough medication in the delayed phase (days 2 - 11 inclusive) of the first cycle of R-CHOP chemotherapy | Days 2 to 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response - Cycle 2 and beyond | Complete response in the acute and delayed phases of each of cycles 2 and beyond of R-CHOP chemotherapy | Day 1 to Day 11 | 
| No Significant Nausea - Cycle 2 and beyond | No significant nausea (defined as a nausea experience score of <2.5cm on a 0 - 10cm visual analogue scale) in the acute and delayed phases of each of cycles 2 and beyond of R-CHOP chemotherapy | Day 1 to Day 11 | 
| Failure of standard anti-emetic prophylaxis, Day 1 to Day 11, Cycle 1 and beyond | Failure of standard anti-emetic prophylaxis in the acute and delayed phase of any one cycle of chemotherapy requiring aprepitant as secondary prophylaxis in subsequent cycles. Failure will be defined as the occurrence of any of the following either during or beyond cycle day 1: One or more episodes of vomiting One or more episodes of nausea requiring the use of 1 or more doses of breakthrough anti-emetics An episode of nausea requiring the use of breakthrough anti-emetics across multiple days An episode of nausea measuring > 2.5cm on a 0 - 10cm visual analogue scale Nausea and/or vomiting that in the clinicians opinion requires use of aprepitant in future cycles | Day 1 to Day 11 | 
| Frequency of common adverse events associated with anti-emetics | Adverse Events (all grades) of the anti-emetic regimen in each cycle of R-CHOP chemotherapy | Day 1 to Day 11 | 
| Severity of common adverse events associated with anti-emetics | Adverse Events (all grades) of the anti-emetic regimen in each cycle of R-CHOP chemotherapy | Day 1 to Day 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Non-Hodgkin, Emesis, Chemotherapy, Nausea, Vomiting, Aprepitant