Impact of an APA Program on EFS in Patients With Diffuse Large-cell B Lymphoma Treated in 1st Line (PHARAOM)

Impact of an Adapted Physical Activity Program on Event-free Survival in Patients With Diffuse Large-cell B Lymphoma Treated in 1st Line

Diffuse large B cell lymphoma is the most common histology of non-Hodgkin's malignant lymphomas (31% of lymphomas), with an incidence of between 15 and 20 new cases per year per 100,000 inhabitants in France. The median age is 65 and a third of patients are over 75 years old. 60% of patients are cured after a standard regimen of chemotherapy with RCHOP; 40% of patients will, however, relapse. No other regimen has shown improvement in overall survival, but poor prognosis factors have been identified. Beyond these factors, other prognostic factors can impact overall and progression-free survival: sarcopenia, nutritional status disorders Sarcopenia is defined by the reduction of muscle mass and strength. It was first described in the elderly and classified as geriatric syndrome such as dementia, falls or frailty. It varies from 5 to 13% between 60 and 70 years and between 11 and 50% beyond 80 years and is classified as primitive, that is to say related to age It can however be secondary to neoplasia. This event has been described in patients with hematologic malignancies during chemotherapy and can reach 55% of patients in the elderly. It is proportional to the intensity of the treatments. It emerges as an independent prognostic factor which is detrimental to survival in these patients. Physical exercise combined with nutritional support could reduce it.

The positive impact of adapted physical activity has been shown in numerous publications on reducing the incidence and risk of relapse for certain cancers (breast, colon prostate). It is less obvious in hematology in view of studies published on adapted physical activity . Adapted physical activity seems to provide a survival benefit in diffuse large cell B lymphoma however the number remains too low in this histology.

Sarcopenia is an often-underestimated event and is associated with older age, co-morbidities, increased infectious complications, and early mortality.

Correcting sarcopenia through appropriate physical activity could reduce its negative prognostic impact.

The aim of the study is to increase the event-free survival of patients in the RCHOP and adapted physical activity arm by 15% compared to the standard arm.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Other: Adapted physical activity

• Study Type: Interventional
• Enrollment (Anticipated): 186
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Magali BALAVOINE; Phone Number: 0033 0241682940; Email: m.balavoine@weprom.fr

Study Locations

• France
  • Besançon, France, 25030
    • Not yet recruiting
    • Chu Jean Minjoz
    • Contact: Adrien CHAUCHET, MD; Phone Number: 0033 0381669024; Email: achauchet@chu-besancon.fr
    • Principal Investigator: Adrien CHAUCHET
  • Le Mans, France, 72000
    • Recruiting
    • Clinique Victor Hugo / Centre Jean Bernard
    • Principal Investigator: Katell Le Dû, MD
    • Contact: Katell LE DÛ, MD; Phone Number: 0033 0243391300; Email: k.ledu@cjb72.org
  • Nancy, France, 54500
    • Not yet recruiting
    • CHRU Nancy
    • Principal Investigator: Pierre Feugier, MD
    • Contact: Pierre FEUGIER, MD; Phone Number: 0033 0383153282; Email: p.feugier@chru-nancy.fr
  • Nantes, France, 44277
    • Recruiting
    • Hôpital Privé du Confluent
    • Contact: Sophie LEBOUVIER-SADOT, MD; Phone Number: 0033 0228272118; Email: sophie.sadot.lebouvier@groupeconfluent.fr
    • Principal Investigator: Sophie LEBOUVIER-SADOT, MD
  • Perpignan, France, 66046
    • Recruiting
    • CH Perpignan
    • Contact: Virginie ROLAND, MD; Phone Number: 0033 0468618907; Email: virginie.roland@ch-perpignan.fr
    • Principal Investigator: Virginie ROLAND, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with diffuse large-cell B lymphoma regardless of the WHO 2016 classification subtype, or low-grade B lymphoma immediately transformed into high-grade B lymphoma (follicular lymphoma of the marginal zone, MALT, lymphocytic, lympho-plasma cells),
2. Treatment naïve or having benefited from 2 cycles of chemotherapy (prephase or COP and cycle n ° 1 of RCHOP) if Performance Status> 3 linked to hemopathy and reversible (≤ 2)
3. Aged ≥ 65 years old,
4. Eligible for treatment with RCHOP, regardless of the IPI score adjusted for age,
5. Performance Status ≤ 2,
6. Patient affiliated to a social security scheme,
7. Patient who has given written consent before any specific procedure related to the study

Exclusion Criteria:

1. Any other type of lymphoma (T lymphoma, Burkitt's lymphoma, non-transformed low-grade B lymphoma, etc.),
2. Cerebral or meningeal damage related to hemopathy,
3. Acquired or congenital motor or sensory deficit which does not allow the completion of APA sessions,
4. Uncontrolled arterial hypertension,
5. Disabling heart or respiratory failure not allowing the completion of APA sessions,
6. Disabling osteo-articular or muscular pathology,
7. LVEF <50%,
8. Patient having received 3 or more cycles of 1st line chemotherapy,
9. Pregnancy or breastfeeding,
10. Active viral infection: hepatitis B, C and HIV,
11. Persons deprived of their liberty or under guardianship
12. Dementia, mental alteration or psychiatric pathology which could compromise the patient's informed consent and / or compliance with the protocol and follow-up of the trial,
13. Patient who can't follow protocol for psychological, social, family or geographic reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard
Experimental: APA; During the first 3 cures, 3 APA sessions will be offered per week:2 sessions of anaerobic type of 1 hour with muscle strengthening, stretching, flexibility and balance, supervised in the room,1 aerobic type exercise session of 1.5 hours (Nordic walking: outdoors) or a 3rd indoor session if not possible,+ home exercise book if the patient so wishes with record the time in minutes per session and the intensity felt and the modalities of the exercises carried out.; During the 5 remaining cycles, 3 APA sessions will be offered per week:1 session of 1 hour in an anaerobic exercise room (muscle strengthening, stretching, flexibility, balance) supervised,1 session of anaerobic exercise per week in autonomy at home (with exercise book),1 or more session per week of one hour of walking or cycling independently at home (aerobic effort) with declaration in the logbook of the intensity of exertion felt and the time in minutes per session.	Other: Adapted physical activity; APA sessions during chemotherapy with aerobic and anaerobic sessions on site and at home (+ home exercises book if the patient so wishes)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To detect an absolute difference of 15% in event-free survival between the 2 groups	Event-free survival will be defined as the time between the date of inclusion and the date of the event or the date of the latest news if the patient is censored.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The compliance with the 72 sessions of APA	Number of sessions performed per patient per part of the program	6 months
The overall physical activity load per patient and per session	Evaluated according to the Foster method (duration of the session in minutes x perceived effort according to the modified Borg scale)	6 months
The overall survival	Time between the date of inclusion and the date of death if the patient is deceased or the date of the latest news if the patient is censored	5 years
The progression free survival	time between the inclusion date and the date of the first examination showing Progression of the disease or the date of death if the patient is deceased or the date of the latest news if the patient is censored	5 years
The progression-free survival after relapse and resumption of therapy	Time between the date of the start of re-treatment and the date of the first examination showing progression of the disease or the date of death if the patient has died or the date of the latest news if the patient is censored,	5 years
The complete and partial response rates	according to Lugano criteria	1 year
The prevalence of complications	Number of patients who presented complication in the numerator and the number of patients followed in the denominator	6 months
The incidence of sarcopenia during follow-up	by CT scan during follow-up will be evaluated by the number of patients with sarcopenia diagnosed during follow-up in the numerator and the number of patients followed in the denominator	2 years
The prevalence of nutritional disorders at diagnosis and at the end of treatment	The number of patients with a disorder of nutritional status in the numerator and the number of patients followed in the denominator,	6 months
The rate of endocrinopathies	Number of patients with endocrinopathy between the inclusion date and the study discharge date in the numerator and the number of patients followed in the denominator	6 months
The rate of second cancers	Number of patients who presented with a second cancer during the study	5 years
The rate of cardiovascular events	Number of patients with a cardiovascular event	5 years
The quality of life of patients	Change from baseline of the European Organisation for Research and Treatment of Cancer quality of life C30 questionnaire score (higher score means better outcome)	5 years
The fatigue of patient	Change from baseline of Multidimensional fatigue inventory score (higher score means worse outcome)	5 years
The depression of patient	Change from baseline of Geriatric depression scale (higher score means worse outcome)	5 years
The cost of hospitalizations	Hospitalizations will be quote (economic data) by medical information department of center	5 years

Collaborators and Investigators

• Sponsor: Weprom

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2021
• Primary Completion (Anticipated): August 1, 2025
• Study Completion (Anticipated): February 1, 2029

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: WP-2020-03; 2019-A02248-49 (Other Identifier: French Health Products Safety Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No