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

NCT04113226 | Unknown Phase 2

• 1 other identifier: PI2018_843_0051
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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

Keywords

chemotherapy; Diffuse large B cell lymphoma (DLBCL); Relapse; activities of patients daily living; Elderly; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups

  at 6 months

• Overall survival rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups

  at 6 months

Study Arms (2)

classical rituximab-based chemotherapy

ACTIVE COMPARATOR

Rituximab-based physician's choice chemotherapy

Drug: Rituximab; Other: Comprehensive Geriatric Assessment (CGA); Other: Activities of daily living (ADL) scale

rituximab plus lenalidomide

EXPERIMENTAL

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.

Drug: Rituximab; Drug: Lenalidomide 20 MG; Other: Comprehensive Geriatric Assessment (CGA); Other: Activities of daily living (ADL) scale

Interventions

Rituximab DRUG

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

classical rituximab-based chemotherapy; rituximab plus lenalidomide

Lenalidomide 20 MG 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

rituximab plus lenalidomide

Comprehensive Geriatric Assessment (CGA) 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.

classical rituximab-based chemotherapy; rituximab plus lenalidomide

Activities of daily living (ADL) scale 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.

classical rituximab-based chemotherapy; rituximab plus lenalidomide

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• Patient able to give his consent and having signed a written informed consent
• Registration in a national health-care system

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

CHU Amiens

Amiens, 80054, France

RECRUITING

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

Rituximab; Lenalidomide; Geriatric Assessment; Activities of Daily Living; Weights and Measures

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Status; Demography; Population Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Frederic Peyrade, MD

  Centre Antoine Lacassagne, Nice

  PRINCIPAL INVESTIGATOR

• Boulhassass, MD

  Hopital Cimiez NICE

  PRINCIPAL INVESTIGATOR

• Soubeyran, Pr

  Institut Bergonié Bordeaux

  PRINCIPAL INVESTIGATOR

• Philippe Caillet, MD

  Hôpital Henri Mondor, APHP CRETEIL

  PRINCIPAL INVESTIGATOR

• Fabrice Jardin, MD

  Centre Henri Becquerel, ROUEN

  PRINCIPAL INVESTIGATOR

• Pascal Chaibi, MD

  Hôpital Charles Foix, APHP IVRY/SEINE

  PRINCIPAL INVESTIGATOR

• Catherine Thieblemont, MD

  Hôpital Saint-louis, APHP, PARIS

  PRINCIPAL INVESTIGATOR

• Damaj, MD

  Centre Hospitalier Universitaire Caen

  PRINCIPAL INVESTIGATOR

• Garidi, MD

  Centre Hospitalier SAINT-QUENTIN

  PRINCIPAL INVESTIGATOR

• Leduc, MD

  Centre Hospitalier Abbeville

  PRINCIPAL INVESTIGATOR

• Dennetière, MD

  Centre Hospitalier COMPIEGNE

  PRINCIPAL INVESTIGATOR

• Ivanoff, MD

  Hôpital Avicenne, APHP BOBIGNY

  PRINCIPAL INVESTIGATOR

• Isabelle Grulois, MD

  CH Saint Malo

  PRINCIPAL INVESTIGATOR

• Margot Robles, MD

  CH Périgueux

  PRINCIPAL INVESTIGATOR

• Caroline DELETTE, PhD

  CHU Amiens Picardie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline Delette, MD

CONTACT

+33 3 22 45 59 14; delette.caroline@chu-amiens.fr

Annabelle BOUSSAULT

CONTACT

+33 3 +33 3 22 45 59 14; boussault.annabelle@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 2, 2019
• Study Start: July 26, 2021
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)