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

Phase 2

Recruiting

• Conditions: Chemotherapy; Diffuse Large B-Cell Lymphoma (DLBCL), Nos; Elderly
• Interventions: Drug: Rituximab; Other: Comprehensive Geriatric Assessment (CGA); Drug: Lenalidomide 20 MG; Other: Activities of daily living (ADL) scale

• Registration Number: NCT04113226
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-10-01
• Study First Submitted QC: 2019-10-01
• Study First Posted: 2019-10-02
• Study Start: 2021-07-26
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-08
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 114

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
classical rituximab-based chemotherapy	Rituximab	Rituximab-based physician's choice chemotherapy
classical rituximab-based chemotherapy	Comprehensive Geriatric Assessment (CGA)	Rituximab-based physician's choice chemotherapy
classical rituximab-based chemotherapy	Activities of daily living (ADL) scale	Rituximab-based physician's choice chemotherapy
rituximab plus lenalidomide	Lenalidomide 20 MG	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)	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	Activities of daily living (ADL) scale	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	Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Progression of free survival at 6 months in elderly patients treated with Rituximab plus Lenalidomide or Rituximab plus chemotherapy.	at 6 months	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 .

Secondary Outcome Measures

Name	Time	Method
Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	at 6 months	Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
Overall survival rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups	at 6 months	Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups

Trial Locations

Locations (1)

CHU Amiens; 🇫🇷 Amiens, France