Relevance of a Web-mediated Follow up in Patients Having a Lymphoma With a High Risk of Relapse in Complete or Partial Response
Phase: NA
Conditions: Lymphoma, T-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Hodgkin
Sponsor: Weprom

SENTINEL Lymphome                                                                ILC-1-2016 
 
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SENTINEL Lymphome 
 
 
 
« Relevance of a Web-mediated Follow up in Patients Having a 
Lymphoma With a High Risk of Relapse in Complete or Partial 
Response» 
 
 
ClinicalTrials.gov: NCT 03154710 
 
Secondary ID: 2016-A01024-47 
Sponsor Ref: ILC-1-2016 
 
 
 
 
Coordinating investigator:   
 
Dr Katell LE DU 
Institut Inter-Régional de Cancérologie – Centre Jean Bernard 
9 rue Beauverger – 72000 LE MANS 
 
 
 
 
 
Scientific Commitee: 
 
Dr Fabrice DENIS                              
Dr Katell LE DU  
Dr Réda BOUABDALLAH                   
Dr Christophe FERME 
Dr Corinne HAIOUN                        
Dr Philippe SOLAL-CELIGNY              
Pr Hervé TILLY 
Dr Olivier LALAUDE 
Pr Olivier TOURNILHAC 
Dr Pauline BRICE 
Dr Olivier CASASNOVAS 
Dr Laurence BRUGIERES 
 
 
 
 
 
 
 
 
Sponsor: 
 
 
WeproM 
 
2 square Gaston Allard 
49000 ANGERS 
Tel: 02 41 68 29 40 
Fax: 02 41 68 29 79 
Head Office : 9 rue Beauverger - 72000 LE MANS 

SENTINEL Lymphome                                                                ILC-1-2016 
 
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TABLE OF CONTENTS 
 
TABLE DES MATIERES ................................................................................................................................... 2 
1. 
STUDY RATIONALE ................................................................................................................................ 3 
1.1. 
LYMPHOMA ......................................................................................................................................... 3 
1.2. 
PATIENT FOLLOW-UP ........................................................................................................................... 3 
1.3. 
MOOVECARE TOOL FOR LYMPHOMA RELAPSE DETECTION ........................................................................ 4 
1.4. 
DESCRIPTION AND JUSTIFICATION OF THE INTERVENTION UNDER STUDY ............................. 5 
1.5. 
BENEFITS ET RISKS ............................................................................................................................... 6 
2. 
OBJECTIVES END ENDPOINT ............................................................................................................... 7 
2.1. 
OBJECTIF ET CRITERE D’EVALUATION PRINCIPAL ................................................................................... 7 
2.2. 
SECONDARY OBJECTIVES AND ENDPOINTS .............................................................................................. 8 
3. 
STUDY DESIGN ....................................................................................................................................... 9 
3.1. 
STUDY METHODOLOGY ......................................................................................................................... 9 
3.2. 
STUDY SCHEMA.................................................................................................................................... 9 
4. 
STUDY POPULATION ........................................................................................................................... 10 
4.1. 
INCLUSION CRITERIA .......................................................................................................................... 10 
4.2. 
NON INCLUSION CRITERIA .................................................................................................................. 10 
5. 
STUDY DESCRIPTION .......................................................................................................................... 11 
5.1. 
BASELINE .......................................................................................................................................... 11 
5.2. 
STUDY EVALUATIONS ......................................................................................................................... 11 
5.3. 
SCHEDULE OF THE STUDY ................................................................................................................... 12 
5.4. 
MOOVCARE WEB-APPLICATION FOLLOW-UP MANAGEMENT .................................................................... 13 
5.5. 
IDENTIFICATION OF ALL SOURCE DATA NOT APPEARING IN THE RECORDS ............................................... 14 
5.6. 
RULES FOR SUBJECT WITHDRAWAL ..................................................................................................... 14 
6. 
DATA MANAGEMENT ET STATISTICS ............................................................................................... 15 
6.1. 
STUDY DATA COLLECTION AND PROCESSING ........................................................................................ 15 
6.2. 
STATISTICS ....................................................................................................................................... 16 
7. 
SAFETY EVALUATION ......................................................................................................................... 18 
7.1. 
DEFINITIONS ..................................................................................................................................... 18 
7.2. 
SERIOUS ADVERSE EVENTS REPORTING ................................................................................................ 19 
7.3. 
MODALITIES AND DURATION OF THE FOLLOW-UP OF PERSONS FOLLOWING THE OCCURRENCE OF ADVERSE 
EVENTS 19 
8. 
ADMINISTRATIVE AND REGULATORY ASPECTS ............................................................................. 20 
8.1. 
RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS .......................................................................... 20 
8.2. 
TRIAL MONITORING ............................................................................................................................ 20 
8.3. 
INSPECTION / AUDIT ......................................................................................................................... 21 
8.4. 
ETHICAL CONSIDERATIONS .................................................................................................................. 21 
8.5. 
COMPETENTE AUTHORITY .................................................................................................................. 21 
8.6. 
CHANGES TO THE PROTOCOL ............................................................................................................. 21 
8.7. 
FUNDING AND INSURANCE .................................................................................................................. 22 
8.8. 
PUBLICATION RULES .......................................................................................................................... 22 
9. 
REFERENCES......................................................................................................................................... 23 
 

 
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1. STUDY RATIONALE 
1.1. LYMPHOMA 
Lymphomas are malignant hemopathies of lymphoid tissue, of ganglionic or extranodal origin. A classic 
distinction is made between Hodgkin's disease (MDH) and Non-Hodgkin's lymphomas (NHL). 
 
Lymphoma is the 6th cancer in terms of incidence in France, where around 11,000 new cases are 
diagnosed each year. Most types of lymphoma are found at all ages with a predominance in the 
elderly. 
 
The most common diagnostic circumstance is detection of malignant lymphoma in the form of a lymph 
node mass. When these lymphadenopathies are deep and voluminous, they can be revealed by the 
presence of various and non-specific symptoms: cough, pleural pain, vena cava depressive syndrome, 
abdominal pain, transit disorders, etc. 
 
Since these tumors are highly chemo-sensitive, treatment is mainly based on chemotherapy: chemo-
immunotherapy for NHL and radio-chemotherapy for Hodgkin's lymphoma. 
 
For "aggressive" lymphomas, current chemotherapy regimens achieve a complete remission rate of 60 
to 80% (1) and a 5-year survival rate of approximately 70%. 
 
Thanks to the continuous improvement of diagnostic techniques and treatments, the prognosis of 
lymphomas is constantly improving. However, 20 to 40% of patients most often relapse within 2 or 3 
years after the end of treatment (2, 3). 
 
In the event of a relapse, the treatment regimen usually offered to patients consists of salvage 
chemotherapy followed by an autologous transplant. 
1.2. PATIENT FOLLOW-UP 
The objectives of post-treatment follow-up are to: 
- detect local or remote recurrences, 
- detect and manage late complications related to treatment as well as sequelae, 
- organize the necessary supportive care, 
- ensure the quality of life 
- early detection of a second cancer. 
 
The current monitoring framework includes a clinical examination and a biological assessment every 
3 months for 2 years and then every 6 months up to 5 years and an imaging assessment every 6 months. 
However, the value of this systematic imaging surveillance is controversial (4-7) and no randomized 
study has been carried out on this subject. Several observational studies suggest that systematic 
imaging surveillance can detect patients with asymptomatic relapse, but none show earlier relapse 
detection (8, 9), nor any difference in survival. 
 
According to Voss et al for patients (children or adolescents) followed for Hodgkin lymphoma in 
remission, the majority of relapses were detected by the appearance of symptoms, clinical 
manifestations or laboratory abnormalities (4, 10-13). 
 
Another problem is the repeated exposure to radiation during each scan with a potentially increased 
risk of a second cancer (15, 16). These imaging tests can also generate anxiety in patients in 
asymptomatic remission, especially just before and while awaiting the results of these tests. Imaging 

 
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assessment can lead to the detection of false positives, which involves performing additional 
examinations, including biopsies that are also painful, expensive and anxiety-inducing (14). 
 
These constraints would be acceptable if the relapse was detected before clinical manifestations and 
allowed patient survival to be increased. 
 
Thompson et al recently published the results of a study regarding the utility of imaging surveillance 
in a large cohort study in patients with diffuse large B-cell lymphoma. Routine imaging surveillance 
allows detection of asymptomatic relapse in only 1.7% of patients (17, 18). 
 
In this context, Huntington et al assessed the medico-economic impact of routine imaging 
surveillance. The results show that the clinical benefit of systematic imaging monitoring of 
asymptomatic patients in remission is very low or even zero compared to the substantial cost incurred 
(19). 
1.3. MOOVECARE TOOL FOR LYMPHOMA RELAPSE DETECTION 
We have developed a score based on the dynamics and the combination of clinical and biological signs 
to alert the doctor of a possible recurrence of lymphoma 
 
The considered clinical symptoms will be self-assessed (presence / absence or no problem / slight 
problem / medium problem / significant problem) by patients every 1 to 2 weeks, sent by their 
Smartphone or computer via the Internet, and will be analyzed by software that determines whether 
or not a relapse or significant complication is likely. The referring doctor will thus be alerted early 
and will summon the patient early for a check-up. 
 
A similar application has been developed to detect relapse of lung cancer early (20, 21). The 
prospective study of this application showed interesting results in these patients with 100% sensitivity, 
89% specificity, 81% PPV and 100% NPV with 11 symptoms studied. In the initial study to establish a 
detection algorithm based on only 6 symptoms, a NPV of 93% was already noted (20). In addition, 
relapses were detected on average 5 weeks before the scheduled date of the follow-up assessment 
(images every 3 months) (21). 
 
An analysis of overall survival (monocentric and non-randomized) in our center also suggests a gain in 
survival of nearly 24% at 1 year (p = 0.02) (22). This gain in survival is most likely related to the early 
initiation of salvage treatment and supportive care. 
 
In the follow-up of the patients, it appeared that the algorithm was more sensitive if the patients 
were not very symptomatic at inclusion and had an initial score of less than 7 (by adding the scores 
of 0 to 3 for the symptoms concerning cough, dyspnea, pain, anorexia and asthenia: no problem = 0, 
mild problem = 1, medium problem = 2, significant problem = 3). A phase 3 study comparing this 
computerized surveillance with surveillance according to the usual method is in progress. 
 
The results of the interim study suggest a favorable trend in overall survival in user and compliant 
patients (use at least once a week): 62% in the standard arm versus 87% in the SENTINEL arm: 
p(logrank)=0,038 (23). 
 
 
 
 
 
 
 
 
 
 
 

 
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Results of the interim analysis of the phase 3 study 
Per-protocol analysis of overall survival (p=0,038). 
1.4. DESCRIPTION AND JUSTIFICATION OF THE 
INTERVENTION UNDER STUDY 
As part of this study, we want to assess the value of web-application monitoring of patients treated 
for lymphoma in complete or partial response. 
 
The underlying assumption is that the use of new information and communication technologies can 
improve the clinical follow-up of patients. To date, access to the Internet and to portable technologies 
is sufficiently wide and democratized to consider the use of this type of telemonitoring in the field of 
health; in particular to facilitate the dissemination of information between the patient and the 
doctor. It is thus possible to imagine using this flow of information to generate alerts, in the particular 
case of the application with the doctor, for example according to the symptoms felt and informed by 
the patient. 
 
Strengthening clinical monitoring in this indication in which routine imaging has not demonstrated its 
value, in particular through the implementation of remote monitoring completed by the patient, may 
present an advantage in terms of efficiency and earliness. support. In fact, in this pathology, up to 
40% of patients relapse early (within 2 to 3 years), in the vast majority of cases symptomatically (less 
than 2% of asymptomatic relapses discovered by imaging); and finally, the current follow-up by 
tomodensitometry every 6 months, which generates costs and radiation exposures for a benefit 
considered rather low, has been carried out in symptomatic patients for several weeks. 
 
In addition, reinforced clinical follow-up can improve the early detection of relapses, and would also 
aim to improve the monitoring of all the significant clinical complications frequent in patients 
suffering from a serious pathology (sepsis, thromboembolism, late iatrogenias, etc. ); if a survival 
benefit is to be hoped for, it will very probably be due on the one hand to the early detection of 
relapses and better control of the relapse through the implementation of early treatments, and on 
the other hand to the management and the early implementation of appropriate supportive care, if 
only through the management of depressive symptoms, or the management of iatrogenic or other 
complications. 
 
However, in a context of increasing health needs and recourse to the health system, but also of 
medical shortage and strict control of health expenditure, strengthening the clinical monitoring of 
patients can only be considered by putting in place implement the means, if they prove to be 
effective, as efficient as possible, particularly in terms of time and costs. In this sense, involving the 
patient and implementing telemedicine solutions now appears very relevant by avoiding unnecessary 
travel and examinations. 

 
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1.5. BENEFITS ET RISKS  
1.5.1. Benefits 
1.5.1.1. 
Individual benefits 
The expected benefit for patients using the Moovecare application will mainly be to have personalized 
follow-up, between 2 consultations. This strengthened clinical follow-up could allow earlier detection 
of a possible relapse or progression of lymphoma, promote early treatment and better control of the 
relapse. It could also improve the detection of possible complications related to treatment or the 
disease but also reduce the anxiety induced by routine surveillance examinations, and thus improve 
the quality of life of patients. 
1.5.1.2. 
Collective benefits 
Beyond the benefit for patients in terms of disease control and quality of life, the use of the 
Moovecare application makes it possible to space out the follow-up by imaging and thus reduce the 
stress and costs caused by the follow-up. standard of patients treated for lymphoma. 
1.5.2. Risks 
1.5.2.1. 
Individual risks 
Constraints 
 
The constraints are minimal and consist in competing: 
- 
for all patients, a quality of life questionnaire and a questionnaire relating to depression at 
inclusion and then at follow-ups at 3, 6, 9 and 12 months 
- 
for patients in the “web app follow up” arm, a satisfaction survey during the 6-month follow-
up and at least every 14 days the specific questionnaire via a computer or a smartphone. The 
entry time is of the order of 1 to 2 minutes. 
 
There is no further examination. 
 
Risks associated with the disease 
 
The risks of natural progression of the disease were not affected by this study. 
1.5.2.2. 
Collective risks 
None 
1.5.3. Benefit/risk balance 
As part of this study, we want to assess the value of web-application monitoring of patients treated 
for lymphoma in complete or partial response. 
 
The web-application follow-up is a reinforced clinical follow-up with which it is unlikely that the 
events (complications or relapses) will be diagnosed later than during standard imaging follow-up. All 

 
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patients will be followed in consultation every 3 months. It is therefore expected that the use of the 
Moovcare app will only benefit patients. 
 
The underlying hypothesis is that a strengthening of clinical monitoring, where the patient can 
regularly inform his doctor about his symptoms, would allow earlier discovery of relapses, and / or 
any other event requiring medical treatment. 
 
A web-application follow-up could thus promote the earlier treatment of relapses and / or other 
medical events occurring during follow-up, and thus improve the survival of patients and their quality 
of life as suggested by the phase study. III in bronchial cancer. 
 
Optimizing clinical follow-up could also favor the spacing out of systematic imaging follow-up, which 
has limitations. This reduction in the frequency of check-ups would benefit the patient by reducing 
his exposure to radiation, but also the benefit of society by reducing the overall cost of monitoring 
patients treated for lymphoma. 
 
2. OBJECTIVES END ENDPOINT 
2.1. OBJECTIF ET CRITERE D’EVALUATION PRINCIPAL 
2.1.1. Primary objective 
The main objective of the study is to show that follow-up via the Moovcare web-application could 
make it possible to better identify the significant complications occurring between two systematic 
follow-up consultations with the specialist in patients followed for high-risk lymphoma. relapse than 
with standard follow-up. The evaluation of the main objective will be carried out over 6 months of 
follow-up. 
2.1.2. Primary endpoint 
The primary endpoint is the appearance of a significant complication detected and confirmed by a 
medical consultation performed outside of standard follow-up. 
 
The significant complications are: 
- 
emergency hospitalization, 
- 
a medical consultation without follow-up with medical prescription (imaging / drug 
prescription) 
- 
a significant event at the classic follow-up consultation (very degraded PS, antibiotic therapy, 
supportive care with consultation, pulmonary embolism, sepsis, severe depression, etc.) 
 
We will identify in the web-app group, the absence of alert in the event of complications and in the 
standard arm, the absence of medical consultation (attending physician) in the event of 
complications. 
 
Complications diagnosed during the follow-up consultation will be reviewed in the form of a list by 
the coordinator, who will rule on the significance of the complication. 

 
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2.2. SECONDARY OBJECTIVES AND ENDPOINTS 
2.2.1. Secondary objectives 
The interest of web-application monitoring will also be assessed in terms of: 
- 
progression-free survival, 
- 
overall patient survival at 2 years, 
- 
estimated time between the diagnosis of a complication, allowed by the application, and the 
theoretical date of the scheduled subsequent follow-up, 
- 
proportion of hospitalization for life-threatening emergencies, 
- 
total number of complications observed, 
- 
quality of life of patients, 
- 
the degree of patient compliance with the use of the web application 
- 
the degree of satisfaction with the use of the web-application and the implementation of 
web-monitoring, 
- 
number of significant complications whatever they may be (but defined above), which have 
arisen and not identified via the application (sensitivity calculation), 
- 
number of significant complications whatever they may be (but defined above), which have 
arisen and identified in the systematic follow-up group, excluding systematic follow-up, 
- 
Performance Status at relapse, 
- 
description of health consumption in the 2 groups. 
2.2.2. Secondary endpoints 
Progression-free survival is defined as the time between the date of the first examination making the 
diagnosis of partial response or complete response and the date of consultation allowing the diagnosis 
of the relapse. 
 
The diagnosis of partial or complete response, as well as relapse in this study follows the definition 
of the Cheson criteria. 
 
The time between the date of diagnosis of the relapse and the nearest consultation date scheduled 
as part of the standard follow-up will be evaluated. The same will be done with the date of diagnosis 
of significant complications. 
 
The time taken to set up a treatment will also be evaluated. Thus, the time between the date of 
diagnosis of each event and the date of implementation of the care (1st psychological consultation, 
date of D1 of treatment, etc.) will be evaluated. 
 
Overall survival is defined as the time between the date of diagnosis of the complete or partial 
response as defined in chapter 2.1.2 and death from any cause within 2 years. 
 
Quality of life will be studied using the QLQ-C30 and HUMEUR PhQ9 questionnaires at inclusion and 
then follow-up consultations at 3, 6, 9 and 12 months. 
 
Patient compliance with the use of the web application will be assessed based on the number of 
assessments completed by patients; an evaluation every 14 days is expected. Patients who have 
completed less than 1 assessment per 42 days (6 weeks) will be considered non-compliant. An overall 
compliance rate over the entire period and a rate per 14-day period can then be presented. 
 
The satisfaction and feelings of patients with regard to the web-monitoring and the use of the web-
application will be assessed by a self-questionnaire during the follow-up visit in the 6th month. 
 
The calculation of the application's sensitivity is based on the evaluation of the number of alerts 
triggered by the application against the results of systematic or alert-triggered imaging examinations. 

 
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The Performance Status will be assessed according to WHO recommendations. 
 
The description of health consumption will be assessed by the number of consultations, imaging and 
laboratory tests performed by the patients in each group. 
3. STUDY DESIGN  
3.1. STUDY METHODOLOGY 
This research is a cohort study, aimed at evaluating the value of web-application monitoring for the 
detection of relapses, and of any other event justifying medical treatment, in patients treated for 
partial response lymphoma. or complete. 
 
It is a multicenter, prospective, longitudinal and randomized study. 
 
3.2. STUDY SCHEMA  
 

 
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4. STUDY POPULATION 
The population concerned includes all patients with lymphoma at high risk of relapse, in follow-up 
for this cancer and having access to the Internet. 
 
We plan to include 80 patients over a 48-month period. 
4.1. INCLUSION CRITERIA 
1) Patient with either: 
a. T-cell lymphoma in first complete or partial response 
b. Hodgkin lymphoma in 2nd complete or partial response including after autograft 
c. c. Large B-cell diffuse lymphoma in 2nd complete or partial response including after 
autograft 
2) End-of-treatment imaging in the last 4 weeks 
3) Age ≥ 18 years 
4) PS ≤2 (WHO) 
5) Patient with an initial symptoms score less than or equal to 5 
6) Patient with internet access and mailbox 
7) Patient affiliated to a social security scheme 
8) Patient with written consent prior to any procedure specific to the study 
4.2. NON INCLUSION CRITERIA 
1) Patient whose lymphoma progressed at the end of the specific treatment (evaluation <3 
months after the end of the previous treatment) 
2) Symptomatic brain or meninges localization 
3) Presence or history of another cancer in the last 3 years, except skin cancers (other than 
melanoma), in situ cancers of the cervix or other cancers considered cured 
4) Persons deprived of their liberty or under trusteeship 
5) Dementia, mental impairment or psychiatric pathology that may compromise the informed 
consent of the patient and / or compliance with the protocol and follow-up of the study 
6) Patients who cannot follow the protocol for psychological, social, family or geographical 
reasons, 
7) Pregnancy or breast-feeding 
8) Patient participating in another interventional study 

 
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5. STUDY DESCRIPTION 
5.1. BASELINE 
Patients eligible for the trial will be required to sign a consent to participate. A patient who has 
already been included in the study cannot be included a second time in the event of a new response 
to the treatment implemented. 
 
For the initial inclusion assessment, certain examination results (extension assessment for a given 
pathology) carried out prior to signing the consent may be used if they were done within the time 
limits requested in the protocol. 
5.1.1. Clinical assessment 
It includes a complete clinical examination (within 2 weeks prior to inclusion) with: 
- 
the history of the disease, 
- 
the evaluation of weight and PS, 
- 
the calculation of the initial score, 
- 
completion of the QLQ-C30 and PhQ-9 quality of life questionnaires. 
5.1.2. Imaging assessment 
It should be less than 4 weeks old at the time of inclusion and start of surveillance and includes a 
thoraco-abdomino-pelvic (TAP) at least (cervical at best) and / or a PET scan. 
5.2. STUDY EVALUATIONS 
The type of follow-up the patient will benefit from will be assigned by randomization. 
 
Patients will be able to benefit from the supportive care adapted to their situations. The need for 
this supportive care can be detected during consultations or through the application. 
 
All patients will be seen in consultation every 3 months with a clinical examination including 
estimation of the PS and a biological assessment (according to the clinician's habits). 
 
The questionnaires (QLQ-C30 and PhQ-9) will be completed again at the 3,6-,9- and 12-month follow-
ups. 
 
For patients randomized to the "standard" arm, a systematic imaging workup (minimum TAP CT 
(cervical at best)) will be performed every 6 months corresponding to standard follow-up. 
 
Patients randomized to the "Web-application follow-up" arm will perform a self-assessment of 
symptoms via the Moovcare application with a maximum interval of 14 days between 2 seizures, and 
if necessary, each time symptoms appear. 
 
In the event of a Moovcare alert (and telephone call to the patient) suggesting a relapse or a 
complication, a CT scan and / or other evaluation examination (PET, biopsies, etc.) will be 
scheduled within ideally less than 14 days depending on the type of alert. 

 
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To be able to connect to the application, included patients will receive personal access codes to the 
application by email with instructions for use: 
- 
access to the application is via a username and password, 
- 
the password is encrypted in the host's database, 
- 
access to the application is via a secure SSL connection (https) which is a protocol for 
securing data exchanges between the client and the application server, 
- 
a brute force intrusion detection system makes it possible, when too many connection 
attempts are detected, to deactivate the account in question. 
 
A satisfaction questionnaire will be taken at the 6-month follow-up. 
5.3. SCHEDULE OF THE STUDY 
For patients randomized to the “standard” arm: 
Baseline 
M3 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
Eligibility criteria 
X 
 
 
 
 
Study presentation / Written inform 
consent 
X 
 
 
 
 
Cancer history 
X 
 
 
 
 
Physical exam 
(PS, weight) 
X 
(- 15 days) 
X 
X 
X 
X 
X 
X 
X 
X 
Biology report (parameters at the 
discretion of the investigator) 
X 
X 
X 
X 
X 
X 
X 
X 
Initial Symptom score 
x 
 
 
 
 
Imaging assessment 
X 
(- 4 weeks) 
 
X 
 
X 
 
X 
 
X 
Quality of life questionnaires 
X 
X 
X 
X 
X 
 
 
 
 
 
For patients randomized to the “web-application follow up” arm: 
Inclusion 
M3 
M6 
M9 
M12 
M15 
M18 
M21 
M24 
Eligibility criteria 
X 
Study presentation / Written 
inform consent 
X 
Cancer history 
X 
Physical exam 
(PS, weight) 
X 
(- 15 days) 
X 
X 
X 
X 
X 
X 
X 
X 
Biology report (parameters at 
the discretion of the 
investigator) 
X 
X 
X 
X 
X 
X 
X 
X 
Initial Symptom score 
x 
Self assessment 
Every 14 days maximum for patients included in the "web application follow-up" arm 
Imaging assessment 
X 
(- 4 weeks) 
In the event of a Moovcare alert or clinical call point 
Satisfaction questionnaire 
X 
Quality of life questionnaires 
X 
X 
X 
X 
X 
 
 
 
 

 
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5.4. MOOVCARE WEB-APPLICATION FOLLOW-UP MANAGEMENT 
The investigator can regularly consult the history of the SENTINEL application. 
In the event of a "suspected" relapse (depending on the answers to the questions), an alert email will 
be sent to the investigator. 
 
In addition, an email will be systematically sent to the investigator if the free text window is filled in 
by the patient. If the symptoms appear not to be serious, the response will be optional, the patient 
being informed of this possibility. If there is any doubt, the investigator will call the patient or even 
summon him. 
 
In the event of a SENTINEL alert, the investigator should: 
1) consult the history of symptoms, 
2) call the patient to verify the absence of entry errors, the absence of a low-calorie diet in case 
of weight loss, and ask the patient about his symptoms 
3) if the doubt is confirmed, summon the patient as soon as possible (ideally <14 days) with an 
initial TAP CT (and cerebral if suggestive clinical signs). 
 
For the most significant symptoms, supportive care may be offered, for example: 
- 
if persistent pain: consultation of algology, 
- 
if weight loss of 3 kg or more and / or anorexia: dietician advice, 
- 
if dyspnea: pneumologic opinion 
- 
if depression: psychologist / psychiatrist advice / psychotropic treatment. 
 
Decision-making tree for Moovcare web -application alerts 
 
 
 
In the event of a relapse or complication, the treatments will be left to the discretion of the 
investigators. The application will be used during the treatment of the relapse or complication at the 
same rate. 

 
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5.5. IDENTIFICATION OF ALL SOURCE DATA NOT APPEARING IN 
THE RECORDS 
The satisfaction and quality of life questionnaires will not be in the patient's source record. They will 
be made available in a pocket per patient in the investigator file so that they can be transcribed in 
the e-CRFs. On the other hand, the self-assessments carried out by the patients will not be in the 
source file, they will be carried out directly on the Moovcare web application. 
 
The other data relating to the patient and necessary for his follow-up outside the trial, will be 
collected in his medical file. 
5.6. RULES FOR SUBJECT WITHDRAWAL  
5.6.1. Criteria for a study subject’s early withdrawal 
Patients can withdraw their consent and request to withdraw from the trial at any time and for any 
reason, without losing the right to be treated by their doctor. The investigator may also prematurely 
discontinue a patient's participation in the trial for any reason that would serve the best interests of 
the patient, including the case of an intercurrent disease or an adverse event. In the event of 
premature discharge, at any time and for any reason, the investigator should notify the patient, if 
necessary, and document the reasons as fully as possible. 
Test exits must be reported in particular for the following possible reasons: 
- 
Death, 
- 
Withdrawal of consent with the patient's request not to use the data already collected, 
- 
Wrongly included, 
- 
Choice of investigator, 
- 
Patient choice, 
- 
No seizure in the application for 6 consecutive weeks apart from a pathology or relapse 
preventing seizure, 
- 
Lost view. 
5.6.2. Procedure for a study subject’s early withdrawal 
The terms of medical care and follow-up in the event of premature discontinuation of the study for a 
given patient will be identical to those usual outside the protocol. 
5.6.3. Study termination criteria (excluding biostatistics considerations) 
The end of the research will be defined as the last follow-up visit (at 24 months) of the last patient 
included. 
 
In addition, the study may be interrupted for administrative reasons, and / or by decision of the 
promoter. If the study is terminated prematurely or suspended, the study leader will immediately 
inform the Ethics Committee of the reason for the termination or suspension. In all cases, the patients 
included will be followed as part of the study until the 24-month follow-up visit by the investigator. 
 

 
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6. DATA MANAGEMENT ET STATISTICS 
6.1. STUDY DATA COLLECTION AND PROCESSING 
6.1.1. Data collection 
An electronic observation log (e-CRF) (ENNOV Clincal®, Cenon, France) will be created per patient. 
All the information required by the protocol will be collected in the e-CRF. It will include the data 
necessary to confirm compliance with the protocol and detect major deviations from the protocol, as 
well as all the data necessary for statistical analyzes. 
 
The person (s) responsible for filling in the e-CRFs (investigator, CRA, etc.) must be defined and 
identified in the table of delegations of responsibilities for each center (kept in the investigative 
workbook). 
6.1.2. Data coding 
By signing this protocol, the principal investigator and all investigators agree to keep confidential the 
identities of the patients who participated in the study. 
 
The information required by the protocol will be collected without mentioning the first and last name 
in the e-CRF with an identification number for the center and a patient number. Only the first letters 
of the patient's first and last name will appear. 
 
This code will be the only information that will appear in the observation notebook (e-CRF) and which 
will allow the e-CRF to be linked to the patient posteriori. 
 
The sponsor is also required to encode the patient data on all documents he may have in his possession 
(reports of imaging examinations, biology, etc.) which would be attached to the e-CRF. 
6.1.3. Data processing 
For each patient, all the data will be collected in the e-CRF. The latter will be completed by the 
investigator and / or the CRA designated for this task. 
 
The processing of the trial data is carried out by the sponsor; the data being the property of WeproM, 
promoter of the research. 
 
The data processing software are ENNOV Clinical® (Cenon, France) and SAS 9.3 (SAS Institute Inc. 
Cary, NC, USA) software. 
 
In accordance with the revision of the Data Protection Act of August 6, 2004 and its implementing 
decree, WeproM has undertaken to follow the MR001 reference methodology of the National 
Commission for Computing and Liberties. 

 
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6.2. STATISTICS 
6.2.1. Description of planned statistical methods 
This study should allow us to evaluate the functioning of the application in a follow-up context in 
patients with lymphoma at high risk of relapse. 
 
The patient sample for this analysis will consist of all patients, included in the study and meeting all 
the eligibility criteria described in Chapter 4, who have signed a consent. 
 
The initial characteristics of the analysis population (demographic data, disease, previous and 
concomitant treatments, prognostic factors, etc.) and all the evaluation criteria described in 
paragraph 2 will be presented globally 
 
For the qualitative variables, we will present the number as well as the percentage. For quantitative 
variables, we will present the median or the mean plus or minus the standard deviation depending on 
the normality of the variable, the minimums and maximums will also be indicated. 
 
Events, as defined in chapter 2.1.2. (apart from relapse) will be described in terms of frequency by 
etiological type (HLT or HLGT according to the MedDRA classification) and by severity according to 
NCI CTCAE v4.02. 
 
For the analysis of the censored data (overall survival and other timeframes of events), the survival 
curves will be plotted according to the Kaplan-Meier estimates, the medians of survival will be 
presented as well as their 95% confidence intervals. 
 
For performing multivariate survival analyzes, the semi-parametric Cox model will be used to 
calculate the odds ratios which will be presented with their 95% confidence interval. 
 
The sensitivity of the application to detect a relapse and / or significant complications will be 
calculated. 
 
Quality of life scores will be calculated according to EORTC guidelines for the QLQ-C30. The quality 
of life will be described at each measurement time and compared to inclusion and then studied 
longitudinally using mixed analysis of variance models for repeated measures. 
PHQ9 scores will be calculated according to the recommendations, described at each measurement 
time and compared to inclusion. The classes proposed in the literature (<= 4; 5-14;> 14) will be used 
to describe the state of depression of patients. 
 
The analyzes will be carried out with SAS 9.3 software (SAS Institute Inc. Cary, NC, USA). 
6.2.1. Sample size determination 
The main objective of the study is to show that follow-up via the SENTINEL 
Lymphoma web-application could make it possible to better identify the 
significant complications occurring between two systematic follow-up 
consultations with the specialist in patients followed for high-risk 
lymphoma. relapse than with standard follow-up. The evaluation of the main 
objective will be carried out over 6 months of follow-up. 
 
This study is based on a pooled triangle test analysis (24, 25, 26). Two 
groups will be composed, one will be monitored via the web-application, the 
other will be monitored in a standard way (consultation and imaging). 
 

 
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A 1: 1 randomization will assign the treatment group to the patient. 
Stratification on center, autologous transplant, PS, relapse and lymphoma 
type will be performed to ensure the comparability of our two populations 
at inclusion. 
 
This sequential method will make it possible to evaluate during recruitment 
the diagnostic efficiency of significant complications outside systematic 
consultations while controlling the power (risk of accepting our null 
hypothesis wrongly) and the type I error (risk of rejecting our wrongly 
null hypothesis). This design allows us to consider stopping the trial as 
soon as the information gathered is sufficient to conclude. We will be able 
to conclude that the web-application is diagnostic efficiently or, on the 
contrary, that it is lacking in interest. 
 
We set the risk of the first species alpha at 5%, the potency at 90%, we 
envisage that monitoring via the web-application allows us to identify 
significant complications between two systematic follow-ups in 90% of 
patients (i.e. 10% of patient presenting an event not identified early) 
against 60% (i.e. 40% of patient presenting an event not identified early) 
in the group followed in a standard way (i.e. a difference of 30%). 
 
The early unidentified event is defined: 
➢ in the web application follow up group by the absence of an alert in the following cases: 
- 
emergency hospitalization, 
- 
a medical consultation without follow-up with medical prescription (imaging / drug 
prescription) 
- 
a significant event at the classic follow-up consultation (very degraded PS, antibiotic 
therapy, supportive care with consultation, pulmonary embolism, sepsis, severe 
depression, etc.) 
 
➢  in the standard group in the following cases: 
- 
emergency 
hospitalization, 
without 
medical 
consultation 
justifying 
this 
hospitalization, 
- 
a significant event at the classic follow-up consultation (very degraded PS, antibiotic 
therapy, supportive care with consultation, pulmonary embolism, sepsis, severe 
depression, etc.). 
 
The events diagnosed during the follow-up consultation will be reviewed, in the form of a list (pooled 
data from the web-application follow-up and standard groups), by the coordinator, who will rule on 
the significance of the event. 
 
- The hypotheses are written: 
 
H0: The proportion of patients without an undiagnosed event outside the systematic consultation 
(follow-up visit and systematic imaging) is not different between the two groups. 
 
H1: The proportion of patients without an undiagnosed event excluding systematic consultation 
(follow-up visit and systematic imaging) is higher with the web-application (by 30%) compared to 
standard follow-up (90% against 60%). 
 
With 2 scheduled analyzes, it is necessary to include a maximum of 40 patients per group. The 
analyzes will be carried out every 2x20 patients included (20 in the control group and 20 in the group 
followed by web-application) 
 
As the inclusions progress, two statistics will be calculated, one reflecting the efficiency and the 
other the amount of information accumulated. The whole will make it possible to draw a decisional 
graph, leaving the area thus drawn a conclusion will be possible. If we find ourselves above the zone 
we will conclude that H0 has been rejected, if we find ourselves below the zone we will conclude 
with an acceptance of H0 and therefore ineffective monitoring via the web-application. 

 
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6.2.3 Randomization 
Randomization 1: 1 will be performed following minimization with stratification on the center, 
autologous transplant, PS, relapse and type of lymphoma. Randomization will be carried out by the 
investigator directly via the electronic CRF developed with ENNOV Clinical® software (Cenon, 
France). 
 
Randomization will only be possible after the main data has been recorded on the e-CRF (date of 
signature of consent, stratification criteria, inclusion and non-inclusion criteria). 
 
The patient's home group will be instantly displayed on the e-CRF after performing the randomization. 
A randomization confirmation email will also be sent to the investigator. 
 
7. SAFETY EVALUATION 
7.1. DEFINITIONS 
7.1.1. Adverse event 
An adverse event is defined as any untoward medical occurrence, in a patient or clinical trial subject 
treated by a medicinal product and which does not necessarily have a causal relationship with this 
treatment. 
 
Severity will be assessed by a qualified physician (Investigator) using the NCI CTCAE version 5.0. The 
intensity of adverse events not listed in this classification will be assessed according to the following 
qualifiers: 
 
- 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
- 
Grade 2: Moderate, minimal local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL). 
- 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL. 
- 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
- 
Grade 5: Death related to the event. 
7.1.2. Unexpected side effect 
An unexpected side effect is an effect the nature, severity, frequency or course of which does not 
match the information on the procedures performed and methods used during the trial. 
 
As part of this research, no AE is expected from the use of the Moovcare application. The AEs expected 
during this study are those related to the disease, to the treatments offered or to the injection of 
contrast product during CT (allergic, cardiovascular, neurosensory, digestive, respiratory, renal, 
thyroid or local effects) reactions. 

 
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7.1.3. Serious adverse event 
A serious adverse event is defined as any untoward medical occurrence or effect that at any dose: 
- 
results in death, 
- 
is life-threatening, 
- 
requires hospitalization or prolongation of existing hospitalization, 
- 
results in persistent or significant disability or incapacity, 
- 
is a congenital anomaly or birth effect. 
 
Will not be considered as SAE: 
- 
hospitalizations for the management of a history, 
- 
outpatient hospitalizations not leading to hospital admission, 
- 
relapse or progression of lymphoma 
- 
deaths linked to the progression of the disease. 
7.2. SERIOUS ADVERSE EVENTS REPORTING 
7.2.1. SAE notification 
Any SAE (except exception specified in the previous paragraph) requires the completion of an SAE 
occurrence report (available in the e-CRF), it was expected or not expected. The investigator must 
check that the information provided on this form is precise and clear (do not use an abbreviation ...). 
 
The SAE must be reported immediately (within 24 hours of its discovery by the investigator) to the 
sponsor via e-CRF and then by fax. 
After receiving the notification of an SUSAR, the promoter declares to the supervisory authorities. 
Once a year, it draws up an annual safety report. 
7.2.2. Independent data monitoring committee 
As the patients were not exposed to any additional risk, it was therefore not considered necessary to 
use an independent monitoring committee in the context of this study. 
7.3. MODALITIES AND DURATION OF THE FOLLOW-UP OF 
PERSONS FOLLOWING THE OCCURRENCE OF ADVERSE EVENTS 
All the patients included in the study are followed for 2 years (24 months).  
 

 
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8. ADMINISTRATIVE AND REGULATORY ASPECTS 
8.1. RIGHT OF ACCESS TO SOURCE DATA AND DOCUMENTS 
The medical data concerning each patient will only be sent to the Sponsor or any person duly 
authorised thereby, and where applicable to the authorised health authorities, under conditions 
guaranteeing the confidentiality of the data. 
The Sponsor and the supervisory authorities may request direct access to medical records to verify 
the clinical trial procedures and/or data, without breaching confidentiality and to the extent 
permitted by the laws and regulations. 
Data collected during the trial may be subject to computer processing in accordance with the CNIL 
requirements (MR001). 
8.2. TRIAL MONITORING  
Monitoring will be provided by WeproM (study sponsor). A Clinical Research Associate (CRA) will visit 
each site regularly to carry out quality control of the data reported in the observation books. 
 
The Protocol has been classified as Risk D (High Risk) according to the definition of the level of 
monitoring based on patient risk and the “LI” score. 
 
 
 
 
Monitoring will be done as follows. 
Each site will be visited at least once, with collection of the following data: 
 
1) The existence of the patients included 
 
2) The collection of signed informed consents and their archiving 
 
3) Compliance with the eligibility criteria (inclusion and non-inclusion) 
 
4) The presence of the primary judgment criterion 
 
5) The declaration and monitoring of Adverse Events 
 
 
a) Serious Adverse Events (SAEs) 
 
 
 
b) Notion of a new fact 
 
6) according to the "level of risk" table: for 20% of patients, the files will be 
monitored at 100%. 
 
The investigator should devote the necessary time to these visits. He must also ensure that the 
monitor has free access to the source documents (that is to say the patient's clinical file, original 
biological and radiological examinations, etc.) which support the data contained in the observation 
book. 

 
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8.3. INSPECTION / AUDIT 
As part of this study, an inspection or audit may take place. The promoter will be in charge of 
preparing this audit or inspection, and ensuring access to all research data and verification of all 
source data. 
8.4. ETHICAL CONSIDERATIONS 
8.4.1. Written Inform Consent 
The investigator undertakes to inform the patient in a clear and fair manner of the protocol and to 
ask him for informed and written consent (information letter and consent collection form attached). 
They will give the patient a copy of the information letter and a consent form. The patient can only 
be included in the study after having read the information letter and having signed and dated the 
consent form. The investigator must also sign and date the consent collection form. The investigator's 
original will be filed in the investigator binder. 
8.4.2. Ethics Committee 
The study project must first be submitted for authorization by an Ethics Committee. The information 
communicated relates, on the one hand, to the methods and nature of the research and, on the other, 
to the guarantees provided for the patients participating in this trial. 
 
The CPP Ouest II of Angers issued a favorable opinion on this research on 08/11/2016. 
8.5. COMPETENTE AUTHORITY 
The ANSM gave its authorization for this research to be carried out on 11/22/2016. 
8.6. CHANGES TO THE PROTOCOL 
Requests for substantial modifications will be sent by the promoter for authorization or information 
to the ANSM and / or to the Ethics Committee concerned in accordance with Law 2004-806 of August 
9, 2004 and its implementing decrees. 
 
The amended protocol should be the subject of a dated updated version. 
Patient information and consent forms should be amended if necessary. 

 
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8.7. FUNDING AND INSURANCE 
Sponsor provides financing for the study and takes out an insurance policy with BiomedicInsure (policy 
n ° 01005345-14058-160056-10005) guaranteeing the pecuniary consequences of its civil liability, in 
accordance with the regulations. 
8.8. PUBLICATION RULES 
A copy of the publication will be given to WeproM, the sponsor of the study, which will necessarily be 
cited. The authors will be determined in proportion to the number of evaluable patients included. 
The coordinating investigator will establish the list of authors. 
 

 
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