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

NCT ID: NCT04113226

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-26
• Study Completion Date: 2024-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

classical rituximab-based chemotherapy

Rituximab-based physician's choice chemotherapy

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

patients ≥ 75 years old with relapsed Diffuse large B-cell lymphoma will be treated with classical Rituximab-based chemotherapy or Rituximab plus Lenalidomide.

Comprehensive Geriatric Assessment (CGA)

Intervention Type: OTHER

A comprehensive geriatric assessment (CGA) is recommended by the Société Internationale d'Onco Gériatrie (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

Intervention Type: OTHER

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.

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Comprehensive Geriatric Assessment (CGA)

Intervention Type: OTHER

A comprehensive geriatric assessment (CGA) is recommended by the Société Internationale d'Onco Gériatrie (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

Intervention Type: OTHER

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.

Interventions

Rituximab

patients ≥ 75 years old with relapsed Diffuse large B-cell lymphoma will be treated with classical Rituximab-based chemotherapy or Rituximab plus Lenalidomide.

Intervention Type: DRUG

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

Intervention Type: DRUG

Comprehensive Geriatric Assessment (CGA)

A comprehensive geriatric assessment (CGA) is recommended by the Société Internationale d'Onco Gériatrie (SIOG) in order to assess all geriatric facets (comorbidity, functional impairment, nutritional status, mental and psychological status, environment,…) on which treatment may impact.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

cimiez hospital Nice

UNKNOWN

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: collaborator

groupe hospitalier public sud de l'oise

UNKNOWN

Sponsor Role: collaborator

Henri Mondor University Hospital

OTHER

Sponsor Role: collaborator

Centre Henri Becquerel

OTHER

Sponsor Role: collaborator

Hôpital Charles Foix

OTHER

Sponsor Role: collaborator

Saint-Louis Hospital, Paris, France

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frederic Peyrade, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Antoine Lacassagne, Nice

Boulhassass, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Cimiez NICE

Soubeyran, Pr

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié Bordeaux

Philippe Caillet, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Henri Mondor, APHP CRETEIL

Fabrice Jardin, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Henri Becquerel, ROUEN

Pascal Chaibi, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Charles Foix, APHP IVRY/SEINE

Catherine Thieblemont, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint-louis, APHP, PARIS

Damaj, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Caen

Garidi, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier SAINT-QUENTIN

Leduc, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Abbeville

Dennetière, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier COMPIEGNE

Ivanoff, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Avicenne, APHP BOBIGNY

Isabelle Grulois, MD

Role: PRINCIPAL_INVESTIGATOR

CH Saint Malo

Margot Robles, MD

Role: PRINCIPAL_INVESTIGATOR

CH Périgueux

Caroline DELETTE, PhD

Role: PRINCIPAL_INVESTIGATOR

CHU Amiens Picardie

Locations

CHU Amiens

Amiens, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Caroline Delette, MD

Role: CONTACT

delette.caroline@chu-amiens.fr

+33 3 22 45 59 14

Annabelle BOUSSAULT

Role: CONTACT

boussault.annabelle@chu-amiens.fr

+33 3 +33 3 22 45 59 14

Facility Contacts

Caroline Delette, MD

Role: primary

delette.caroline@chu-amiens.fr

Other Identifiers

PI2018_843_0051

Identifier Type: -

Identifier Source: org_study_id