The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in patients aged 80 years old or more with not previously treated cluster of differentiation antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival (OS).The SENIOR trial will evaluate the tolerance and efficacy of the combination of the R2-miniCHOP regimen and compare this experimental arm to the standard R-miniCHOP regimen.The statistical plan is based on the hypothesis of an increase by 15% of the 2y-OS in favor of the experimental arm, as compared to the reference arm (R-miniCHOP).
The purpose of this study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP (Sub-cutaneous Rituximab-miniCHOP) in patients aged 80 years old or more with not previously treated cluster of differentiation antigen 20 positive (CD20+) diffuse large B-cell lymphoma as measured by the overall survival (OS). Primary endpoint of the study is to compare the efficacy of R2-miniCHOP (Sub-cutaneous Rituximab-miniCHOP + lenalidomide) and R-miniCHOP ((Sub-cutaneous Rituximab-miniCHOP) in patients of 80 years old or more with not previously treated CD20+ diffuse large B-cell lymphoma as measured by the overall survival (OS). Secondary endpoints are: * To evaluate the efficacy and the safety of R2-miniCHOP as measured by the PFS (Progression Free Survival), EFS (Event Free Survival), the DoR (duration of response), the DFS (disease free survival), response rate at the end of the treatment, the additional toxicities * To evaluate the simplified scale prognostic impact (IADL, MNA, G8, CIRS-G) * To assess the quality of life before and after treatment This study is a multicentric, phase III, open-label, randomized (1:1) trial evaluating the efficacy of R2-miniCHOP in patients aged of 80 years or more with non-previously treated CD20+ diffuse large B-cell lymphoma (age-adjusted IPI= 0 to 3), Ann Arbor stage II to IV with a performance status ECOG from 0 to 2. This study includes a run in phase to assess feasibility, safety and tolerance of subcutaneous rituximab injections and oral lenalidomide (10 mg D1-D14) in combination with dose-reduced intensity CHOP regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
ZNA Stuivenberg
Antwerp, Belgium
A. Z. Sint-Jan
Bruges, Belgium
Institut Jules Bordet
Brussels, Belgium
Université Catholique de Louvain Saint Luc
Brussels, Belgium
Hôpital Erasme
Brussels, Belgium
Grand Hôpital de Charleroi
Charleroi, Belgium
The overall survival (OS)
OS will be measured from the date of randomization to the date of death from any cause. Alive patients will be censored at their last contact.
Time frame: OS rates at 2 years
Progression-Free Survival (PFS)
PFS is defined as the time from randomization into the study to the first observation of documented disease progression/relapse or death due to any cause. If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment.
Time frame: PFS rates at 2 years
Event-Free Survival (EFS)
EFS will be measured from the date of randomization to the date of first documented disease progression/relapse (Cheson 1999), initiation of new anti-lymphoma therapy or death from any cause. Patients without documented event at the time of analysis will be censored at their visit with adequate assessment.
Time frame: EFS rates at 2 years
Duration of Response (DoR)
DoR will be measured from the time of attainment of Complete Response/unconfirmed Complete Response (CR/CRu) or Partial Response (PR) to the date of first documented disease progression/relapse or death from any cause. Patients alive and free of progression will be censored at their last visit with adequate assessment.
Time frame: DoR rates at 2 years
Disease-Free Survival (DFS)
DFS will be measured from the date of attainment of a complete or unconfirmed complete response (at the end of treatment or at permanent treatment discontinuation evaluation) to the date of first observation of documented disease progression or death due to any cause. Complete Response/unconfirmed Complete Response (CR/CRu) patients who have not progressed or died will be censored at the time of last visit with adequate assessment.
Time frame: DFS rates at 2 years
OS according to GCB/non-GCB phenotype
OS will be described for the R2-miniCHOP group according to Hans algorithm (GCB/non-GCB phenotype).
Time frame: OS according to GCB/non-GCB phenotype rates at 2 years
Response Rate at the end of treatment
Disease response evaluation at end of treatment (after 6 cycles) will be used to determine the Response Rate. Response will be assessed at end of treatment (after end of the 6th cycle of treatment or at permanent treatment discontinuation). Assessment of response will be based on the International Workshop to Standardize Response criteria for non-Hodgkin's lymphoma (NHL) (Criteria for evaluation of response in NHL (Cheson, 1999)).
Time frame: 22 weeks (28 days after the end of the 6, three-weeks interval, cycles of treatment) or within 28 days following permanent treatment discontinuation
Simplified Geriatric Scales
Four geriatric tools will be performed before any chemotherapy administration (Instrumental Activities of Daily Living (IADL), Mini Nutritional Assessment (MNA), G8, and Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scales). Each scale will be analyzed in order to have a picture of the population at baseline. Thereafter, the prognosis impact in OS and PFS of each scale will be evaluated using univariate (Kaplan Meier) and multivariate analyses (Cox model). Safety analyses will also be performed according to each scale in order to evaluate the toxicity predictive power of these scales.
Time frame: At baseline
Health related Quality of Life (HRQOL)
HRQOL will be assessed by the Quality of Life Questionnaire-C30 and Elderly14 (QLQ-C30 and the QLQ-ELD14) at randomization and at end of treatment. The improvement or not of the QoL will therefore be assessed. The QLQ-ELD14 was developed to supplement the QLQ-C30 for measuring HRQoL in patients aged \>70 years in oncology studies.
Time frame: At randomization and 22 weeks after Day 1 of Cycle 1 of R-miniCHOP or R2-miniCHOP (28 days after the end of the 6, three-weeks interval, cycles of treatment)
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Universitair Ziekenhuis Gent
Ghent, Belgium
AZ Groeninge
Kortrijk, Belgium
CHR Citadelle
Liège, Belgium
CHU de Liège
Liège, Belgium
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