Assessment of Survival and Autonomy With Rituximab Plus Chemotherapy or Rituximab Plus Lenalidomide for Elderly Patients With Relapsed Diffuse Large B-cell Lymphoma

Elderly Clinical Trial

— Relyage  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04113226
• Other study ID #: PI2018_843_0051
• Status: Recruiting
• Phase: Phase 2
• Start date: July 26, 2021
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: Caroline Delette, MD
• Phone: +33 3 22 45 59 14
• Email: delette.caroline[@]chu-amiens.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy
• Diffuse Large B-Cell Lymphoma (DLBCL), Nos
• Elderly
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
patients = 75 years old with relapsed Diffuse large B-cell lymphoma will be treated with classical Rituximab-based chemotherapy or Rituximab plus Lenalidomide.
• Lenalidomide 20 MG
patients = 75 years old with relapsed Diffuse large B-cell lymphoma will be treated with Rituximab plus Lenalidomide. Four 28-days cycles of oral Lenalidomide (20 mg / d for 21 days) and Rituximab 375mg/m2 on day 1 and day 21. After this induction phase, patients achieving at least stable disease were given lenalidomide maintenance therapy (20 mg for 21 days) until progression

Other:
• Comprehensive Geriatric Assessment (CGA)
A comprehensive geriatric assessment (CGA) is recommended by the Socie´te´ Internationale d'Onco Ge´riatrie (SIOG) in order to assess all geriatric facets (comorbidity, functional impairment, nutritional status, mental and psychological status, environment,…) on which treatment may impact.
• Activities of daily living (ADL) scale
Activities of daily living (ADL) comprise the basic actions that involve caring for one's self and body, including personal care, mobility, and eating. The Index ranks adequacy of performance in the six functions of bathing, dressing, toileting, transferring, continence, and feeding. Clients are scored yes/no for independence in each of the six functions. A score of 6 indicates full function, 4 indicates moderate impairment, and 2 or less indicates severe functional impairment.

Locations

Country	Name	City	State
France	CHU Amiens	Amiens

Sponsors (8)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens	Centre Henri Becquerel, cimiez hospital Nice, groupe hospitalier public sud de l'oise, Henri Mondor University Hospital, Hôpital Charles Foix, Institut Bergonié, Saint-Louis Hospital, Paris, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of free survival at 6 months in elderly patients treated with Rituximab plus Lenalidomide or Rituximab plus chemotherapy.	Progression of free survival at 6 months with maintain autonomy without loss of 0.5 point of ADL in elderly patients 75 years old and over with relapsed diffuse large B-cell lymphoma treated with Rituximab plus Lenalidomide or Rituximab plus investigator's choice .	at 6 months
Secondary	Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	at 6 months
Secondary	Overall survival rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	at 6 months