CLINICAL STUDY FINALIZED TO DETERMINE THE EFFICACY AND SAFETY OF STANDARD TREATMENT WITH THE LENALIDOMIDE E DEXAMETHASONE DRUGS COMPARED WITH THE DOSE REDUCTIONS IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA THAT CAN NOT RECEIVE THE STANDARD CHEMIOTHERAPY

Phase 1

Conditions: ELDERLY AND UNFIT NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS
MedDRA version: 18.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-004166-33-IT

Lead Sponsor: FO.NE.SA.Onlus

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 200

Inclusion Criteria

-Patients >65 years unfit and unsuitable, according to the investigator’s opinion, to receive approved first line treatments for newly diagnosed MM.
-Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
-Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
-Symptomatic MM based on standard CRAB criteria (5).
-Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, = 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results.
-All randomized patients will be selected based on the use of 3 geriatric scales: IADL, ADL, Charlson. Unfit patients with clinical sign of frailty (mild, moderate or severe frailty), including need help for household tasks and personal care can be enrolled in this trial (2,4).
-In order to include patients who normally are not select for clinical trials, also patients with the following abnormal laboratory values can be considered:
a)absolute neutrophil count (ANC) < 1 x 10^9/L
b)platelet count < 80 x 10^9/L
c)haemoglobin < 8 g/dl.
d)aspartate transaminase (AST): < 5 x the upper limit of normal (ULN).
e)alanine transaminase (ALT): < 5 x the ULN.
f)total bilirubin: > 1.5 x the ULN
g)calculated or measured creatinine clearance: <30 mL/minute

The geriatric assessment evaluations will select unfit patients to be randomized regardless of possible abnormal laboratory values at the study entry.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

-Pregnant or lactating females.
-Male patients not agreeing to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
-Females of childbearing potential not agreeing to use two acceptable methods for contraception (e.g. a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
-Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days).
-Any significant medical disease or conditions that, in the investigator’s opinion, may interfere with protocol adherence or subject’s ability to give informed consent or could place the subject at unacceptable risk.
-Presence of clinical active infectious hepatitis type B or C, classified into Child-Pugh class C (see Appendix V).
-Presence of acute active infection requiring antibiotics or infiltrative pulmonary disease.
-Contraindication to any of the required drugs or supportive treatments.
-Presence of prior history of malignancies, other than multiple myeloma, with a life expectancy < 2 years.
-Known allergy to any of the study medications, their analogues, or excipients in the various formulations.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy and the safety of the standard Rd schedule (arm A) versus an experimental approach including the standard Rd regimen as induction, followed by lenalidomide alone as maintenance (arm B).;Secondary Objective: To compare additional efficacy outcome as overall survival, overall responses and quality of life.;Primary end point(s): Event-free survival defined as:<br>•Progression<br>•Death for any cause<br>•Discontinuation of lenalidomide therapy<br>•Occurrence of any haematological grade 4 or non-haematological grade 3-4 adverse events (AES), including Secondary Primary Malignancies (SPMs);Timepoint(s) of evaluation of this end point: 2 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Progression-free survival (PFS)<br>•Overall survival (OS)<br>•Time to progression (TTP)<br>•Overall response rate (ORR)<br>•Time to response (TTR)<br>•Duration of response (DOR)<br>•Time to the next therapy (TNT)<br>•Incidence of dose reduction and drug discontinuation<br>•Health care cost and quality of life assessment (HRQOL)<br>•Modification of response and outcome in subgroups with different prognosis according to current prognostic factors;Timepoint(s) of evaluation of this end point: 5 years