Revlimid And Prednisone Followed By Revlimid, Melphalan And Prednisone In Multiple Myeloma Patients

A Multicenter, Open Label Study Of Oral Revlimid And Prednisone (Rp) Followed By Oral Revlimid Melphalan And Prednisone (Mpr) In Newly Diagnosed Elderly Multiple Myeloma Patients

This study will determine whether the association of Revlimid and Prednisone (RP) as induction treatment followed by Revlimid, Melphalan and Prednisone (MPR) as consolidation treatment is safe and induce a significant rate of PR (and CR) in newly diagnosed elderly MM patients.

This phase II study is a multicenter, open label trial designed to determine whether the association of Revlimid and Prednisone (RP) as induction treatment followed by Revlimid, Melphalan and Prednisone (MPR) as consolidation treatment is safe and induce a significant rate of PR (and CR) in newly diagnosed elderly MM patients.

This study consists of 3 phases for each study subject: Pre-treatment, Treatment, long-term follow-up (LTFU).

Pre-treatment period: after providing written informed consent, patients will undergo screening for protocol eligibility as outlined in the Schedule of Study Assessments.

Treatment period: includes induction, consolidation and maintenance.

Induction regimen:Patients will start induction treatment with association of Lenalidomide and Prednisone (RP).

Consolidation regimen After the completion of the 4 RP cycles therapy will continue with the MPR association:·

According to the results after the first stage the decisions are as follows: 1. The study may continue to a second stage, at the same dose of lenalidomide of MPR cycles, if grade 3-4 adverse events are 25-50% and PR > 50%;

2. The study may be stopped (if PR < 40% and grade 3-4 adverse events > 25-30%)

3. A new first stage may be started:

• At an increase dose of Lenalidomide administered in advanced MPR cycles if grade 3-4 adverse events are < 25-30%, independently from efficacy;
• At a reduced dose of Lenalidomide administered in advanced MPR cycles if grade 3-4 adverse events are > 50% and PR rate > 50%

Maintenance: Within 3 months from the last MPR cycle, therapy will continue with RP as maintenance.

Each cycle will be repeated every 28 days, until PD.

Inclusion Criteria:

• Patient is 65 years of age or older at the time of signing the informed consent.
• 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.
• 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.
• Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method)(Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy.
• Patient was a newly diagnosed multiple myeloma based on standard criteria
• Patient has measurable disease, defined as follows: - Secretory myeloma: 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; - Non-secretory myeloma: > 30% plasma cells in the bone marrow and at least one plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
• Patient has a Karnofsky performance status ≥ 50%.
• Patient has a life-expectancy >3 months.

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from signing the informed consent form or placed the subjects at unacceptable risk.
• 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).
• Pregnant or lactating females
• Known positive for HIV or active infectious hepatitis type A, B or C