A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THEEFFICACY AND SAFETY OF CYCLOPHOSPHAMIDE, LENALIDOMIDE AND DEXAMETHASONE (CRD) versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS

• Conditions: Multiple Myeloma

• Registration Number: EUCTR2008-008599-15-CZ
• Lead Sponsor: FONDAZIONE NEOPLASIE SANGUE ONLUS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-11
• Last Update Posted: 2 May 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

-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of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without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. -Patient is 65 years old or younger at the time of signing the informed
consent
-Women of child-bearing potential must agree to use 2 methods of contraception: 1 effective (for example
hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before
starting the therapy, during the Treatment Period, and for 4 weeks after the last dose of lenalidomide
-Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug
therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy.
-Negative serum B-human chorionic gonadotropin (B-HCG) pregnancy test both 24 hours prior to beginning of
therapy and then at 4 weeks intervals in women with regular menstrual cycles or every 2 weeks in women with
irregular menstrual cycles during study treatment for subjects of childbearing potential
-Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (10), and has measurable
disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily,
greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable,
urine light-chain excretion of >200 mg/24 hours; measurable plasmacytoma > 2 cm as determined by clinical
examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells >10%.
-Patient has a Karnofsky performance status more than 60%.
-Patient has a life-expectancy > 6 months -Patient has HBV, HCV and HIV negative
test.
-Patients must have normal ECG and NYHA more than 2; an evaluation of ejection fraction by ECHO or MUGA
is optional -Patients must normal chest X ray; an evaluation of pulmonary function studies on mechanical aspects
(FEV1, FVC, etc) and diffusion capacity (DLCO) is optional.
-Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1): *Platelet
count more than 75 x 109/L without transfusion support within 7 days before the test. *Absolute neutrophil
count (ANC) 1.5x 109/L without the use of growth factors. *Corrected serum calcium more than 14 mg/dL
(3.5 mmol/L).*Aspartate transaminase (AST): more than 2.5 x the upper limit of normal (ULN). *Alanine
transaminase(ALT): more than 2.5 x the ULN. *Total bilirubin: more than1.5 x the ULN. *Calculated or
measured creatinine clearance: 20 mL/minute
-Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually
centralized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-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 serious medical condition, including the presence of laboratory abnormalities, which places the subject at
an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data
from the study.
-Pregnant or lactating women. A serum b-hCG pregnancy test must be performed at the Screening visit, for
female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study.
Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test
with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug
delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses
at any time in the preceding 24 consecutive months) or surgically sterilised women (hysterectomy, bilateral
ovariectomy, bilateral salpingectomy);
-Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for 3
years. Exceptions include the following: basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancer
(TNM stage of T1a or T1b)
-Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the
latest 12 months.

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 of the combination of lenalidomide with low-dose alkylating agents versus high-dose<br>melphalan in newly diagnosed, symptomatic MM patients.;Primary end point(s): Progression free survival (PFS);Secondary Objective: To assess the safety of lenalidomide with low-dose alkylating agents compared to high-dose melphalan in<br>newly diagnosed, symptomatic MM patients. - To assess the prognostic value of risk factor at diagnosis (b2-<br>microglobulin, albumin, C-reactive protein, cytogenetics).<br>To assess the efficacy and safety of lenalidomide as maintenance treatment after the consolidation phase.<br>To assess prognostic significance of stringent remission evaluated by free light chain assay.