Clinical trial NCT04113226: Assessment of Survival and Autonomy With Rituximab Plus Chemotherapy or Rituximab Plus Lenalidomide for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma
Official title: Assessment of Survival and Autonomy With Rituximab Plus Chemotherapy or Rituximab Plus Lenalidomide for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chemotherapy
Diffuse Large B-Cell Lymphoma (DLBCL), Nos
Elderly
Keywords: chemotherapy
Diffuse large B cell lymphoma (DLBCL)
Relapse
activities of patients daily living
Elderly
Lenalidomide
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
Collaborators: name: cimiez hospital Nice
name: Institut Bergonié
name: groupe hospitalier public sud de l'oise
name: Henri Mondor University Hospital
name: Centre Henri Becquerel
name: Hôpital Charles Foix
name: Saint-Louis Hospital, Paris, France
First posted: 2019-10-02
Enrollment: 114
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Annual incidence increases with age and achieves more than 30 per 100 000 patients 65 years old or over.

Despite high response rates with conventional regimen as R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone), 30% to 40% of patients develop a relapse or a refractory disease, with a poor prognosis. There is no standard chemotherapy in second line for elderly patients, which are not eligible to receive a salvage treatment by high-dose therapy followed by autologous stem cell transplantation. The median progression-free-survival (PFS) is less than one year with the most commonly used regimens including R-Gemcitabine-Oxaliplatin (R-GEMOX) and R-Bendamustine. One the other side, Rituximab plus Lenalidomide, an immunomodulatory agent, is an active new therapeutic approach, with an efficacy proved in a phase II trial with a patients with a prolonged disease-free-survival of 32 months for responders in patients with a median age of 74 years old. This combination is also efficient in the ABC phenotype DLBCL which is more common in elderly patients.

For elderly patients, a management of the geriatric impairment together with lymphoma is required. Indeed, a comprehensive geriatric assessment detects frailty and vulnerability in elderly with a lymphoma and predicts severe treatment related toxicity, treatment settings and progression free survival. Moreover, geriatric intervention improved outcome, autonomy and quality of life. Functional status, assessed by Activities of patients Daily Living (ADL) is an independent predictive factor for feasibility of chemotherapy in elderly patients with cancer. The mini Data Set of DIALOG group is a new simplified geriatric assessment for oncologist.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 75 years old
* Histologically proven CD20+ diffuse large B-cell lymphoma (DLBCL) (WHO classification 2008) including all clinical subtypes (primary mediastinal, intravascular, etc...), with all aaIPI. May also be included : transformed DLBCL from low grade lymphoma (Follicular, other...) and DLBCL associated with some small cell Infiltration in bone marrow or lymph node or CD20+ B-cell lymphoma, with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma or CD20+ Follicular lymphoma grade 3B or CD20+ Aggressive B-cell lymphoma unclassifiable
* Relapse ≥ 6 months
* ADL ≥ 2
* Negative HIV, HBV (anti-HBc negativity) and HCV serologies test within 4 weeks before inclusion
* Patient able to give his consent and having signed a written informed consent
* Registration in a national health-care system

Exclusion Criteria:

* Central nervous system or meningeal involvement by lymphoma
* Poor renal function (creatinine clearance \< 30 ml/min, according to MDRD formula)
* Poor hepatic function (total bilirubin level\>30mmol/l, transaminases \>2.5 maximum normal level) unless these abnormalities are related to the lymphoma
* Neuropathy grade \> 1
* Poor bone marrow reserve as defined by neutrophils\<1.5 G/l or platelets\<100 G/l, unless related to bone marrow infiltration
* Other concomitant or previous malignancy, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for \<5 years
* Other serious and uncontrolled non-malignant disease.
* Insufficient proficiency of the French language and disability to complete a questionnaire
* Patient under guardianship

Primary outcomes:
measure: Progression of free survival at 6 months in elderly patients treated with Rituximab plus Lenalidomide or Rituximab plus chemotherapy.
timeFrame: at 6 months
Secondary outcomes:
measure: Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
timeFrame: at 6 months
measure: Overall survival rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
timeFrame: at 6 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
Study officials:
affiliation: Centre Antoine Lacassagne NICE
name: Frederic Peyrade, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Cimiez NICE
name: Boulhassass, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Bergonié Bordeaux
name: Soubeyran, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Henri Mondor, APHP CRETEIL
name: Philippe Caillet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Henri Becquerel, ROUEN
name: Fabrice Jardin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Charles Foix, APHP IVRY/SEINE
name: Pascal Chaibi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint-louis, APHP, PARIS
name: Catherine Thieblemont, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Caen
name: Damaj, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier SAINT-QUENTIN
name: Garidi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Abbeville
name: Leduc, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier COMPIEGNE
name: Dennetière, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Avicenne, APHP BOBIGNY
name: Ivanoff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Saint Malo
name: Isabelle Grulois, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CH Périgueux
name: Margot Robles, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Amiens Picardie
name: Caroline DELETTE, PhD
role: PRINCIPAL_INVESTIGATOR
References: