| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification), in patients aged ≥80 years and not previously treated. |
|
| E.1.1.1 | Medical condition in easily understood language |
| B lymphoma in patients of 80 years old or more, not previously treated. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10012818 |
| E.1.2 | Term | Diffuse large B-cell lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary objective of the study is to compare the efficacy of R2-miniCHOP and R-miniCHOP in patients ≥ 80 years with not previously treated CD20+ diffuse large B-cell lymphoma as measured by the overall survival (OS)
|
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives 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
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- Evaluation of the impact of anthropometric measures obtained by CT-scan including sarcopenia index and subcutaneous fat mass on chemotherapy response
- Proteomic and genomic studies will be encouraged for exploratory purposes to identify new markers of disease and new markers that could predict response to therapy |
|
| E.3 | Principal inclusion criteria |
Patients must satisfy all following criteria to be enrolled in the study:
1. Patient with 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:
- De Novo 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
2. With a CD10 immunostaining performed by the participating center pathologist
3. Aged ≥ 80 years old
4. Ann Arbor stage II, III or IV
5. Patient previously untreated for DLBCL
6. ECOG performance status ≤ 2
7. With a minimum life expectancy of 3 months
8. Negative HIV, HBV and HCV serologies test within 4 weeks before inclusion (except after hepatitis B vaccination or for patients who are HBs Ag negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative)
9. Patient able to give his consent and having signed a written Informed consent
10. Patient affiliated to social security system, if applicable
11. Male patients must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 3 months following study drug discontinuation, even if they have undergone a successful vasectomy
12. All patients must agree to fulfill the global Lenalidomide Pregnancy Prevention Risk Management Plan as applicable according to the randomization arm (experimental arm) |
|
| E.4 | Principal exclusion criteria |
Presence of any of the following will exclude a patient from enrollment:
1. Any other histological type of lymphoma, Burkitt included
2. Any history of treated or non-treated small-B cell lymphoma
3. Central nervous system or meningeal involvement by lymphoma
4. Contra-indication to any drug contained in the chemotherapy regimens ; for anthracycline use, ejection fraction should be > 50%
5. Any serious active disease (according to the investigator’s decision)
6. History of deep venous thrombosis or arterial thromboembolism events within the past 12 months before inclusion
7. Poor renal function (creatinine clearance < 40 ml/min, according to MDRD formula)
8. Poor hepatic function (total bilirubin level >30 µmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma
9. Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration
10. Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma Patients previously diagnosed with prostate cancer are eligible if (1) their disease was T1-T2a, N0, M0, with a Gleason score ≤7, and a
prostate specific antigen (PSA) ≤10 ng/mL prior to initial therapy, (2) they had definitive curative therapy (i.e., prostatectomy or radiotherapy) 2 years before Day 1 of Cycle 1, and (3) at a minimum 2 years following therapy they had no clinical evidence of prostate cancer, and their PSA was undetectable if they underwent prostatectomy or <1 ng/mL if they did not undergo prostatectomy
11. Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study
12. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy
13. Prior use of lenalidomide
14. Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide
15. Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide
16. Subjects with ≥ Grade 2 neuropathy
17. Adult patient under tutelage
18. Female of childbearing potential are excluded. (Note: Females are defined as not of childbearing potential if there is documentation of “natural menopause for at least 24 consecutive months, a hysterectomy or bilateral oophorectomy”) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the overall survival (OS).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Overall survival 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. |
|
| E.5.2 | Secondary end point(s) |
- Progression-Free Survival (PFS)
- Event-Free Survival (EFS)
- Duration of Response (DoR)
- Disease-Free Survival (DFS)
- Response Rate at the end of the treatment (after end of the 6th cycle of treatment or at premature withdrawal) will be assessed using disease response evaluation at end of treatment, according to Cheson 1999
- Simplified geriatric scale, based on four geriatric tools that will be performed before any chemotherapy administration (IADL, MNA, G8, and CIRS-G scales) will be analyzed in order to have a picture of the population at baseline, to evaluate the prognosis impact in OS and PFS of each scale and to evaluate the toxicity predictive power of these scales
- Health related Quality of Life will be assessed by the QLQ-C30 and the QLQ-ELD14 at randomization and at end of treatment. The improvement or not of the QoL will therefore be assessed. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS : time from randomization to the first observation of documented disease progression/relapse or death due to any cause.
EFS : 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.
DoR : measured from the time of attainment of CR/CRu or PR to the date of first documented disease progression/relapse or death from any cause.
DFS : measured from the date of attainment of CR/CRu (at the end of treatment or at withdrawal evaluation) to the date of first observation of documented disease progression or death due to any cause.
Four geriatric tools : before any chemotherapy administration.
HRQoL assessed at randomization and at end of treatment. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 100 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined as the last patient's last visit and will occur approximately 4.5 years at the latest after the first patient is randomized. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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