Clinical Trials /

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

NCT04113226

Description:

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.

Related Conditions:
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Grade 3b Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PI2018_843_0051
  • NCT ID: NCT04113226

Conditions

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

Interventions

DrugSynonymsArms
Rituximabclassical rituximab-based chemotherapy
Lenalidomide 20 MGrituximab plus lenalidomide

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
classical rituximab-based chemotherapyActive ComparatorRituximab-based physician's choice chemotherapy
  • Rituximab
rituximab plus lenalidomideExperimentalFour 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
  • Lenalidomide 20 MG

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:75 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression of free survival at 6 months in elderly patients treated with Rituximab plus Lenalidomide or Rituximab plus chemotherapy.
Time Frame:at 6 months
Safety Issue:
Description: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

Measure:Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
Time Frame:at 6 months
Safety Issue:
Description:Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
Measure:Overall survival rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups
Time Frame:at 6 months
Safety Issue:
Description:Response rate in Rituximab plus Lenalidomide and Rituximab plus chemotherapy groups

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Centre Hospitalier Universitaire, Amiens

Trial Keywords

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

Last Updated

October 1, 2019