RMPT for Relapsed/Refractory Multiple Myeloma

1. Patient is of a legally consenting age as defined by local regulations.
2. Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements.
3. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
4. 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.
5. 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.

6. Patient was previously diagnosed with symptomatic multiple myeloma based on standard criteria (12), and 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 > 2cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
7. Patient is relapsed or refractory after one or two lines of treatment
8. Patient has a Karnofsky performance status ≥ 60%.
9. Patient has a life-expectancy > 3 months.

10. Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):

    • Platelet count ³ 100 x 109/L without transfusion support within 7 days before the test
    • Absolute neutrophil count ³ 1.0 x 109/L without the use of growth factors
    • Total bilirubin £ 1.5 x the ULN
    • AST (SGOT) and ALT (SGPT) £ 2.5 x ULN
    • Corrected serum calcium \< 14 mg/dl (3.5 mmol/L)
    • Calculated or measured creatinine clearance: ≥ 20 mL/minute

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or beast feeding females.
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Use of any other concomitant standard/experimental anti-myeloma drug or therapy
5. Prior induction therapy with R-MP or M-PT association

6. Any of the following laboratory abnormalities:

   • Platelet count \< 100 ´ 109/L.
   • Absolute neutrophil count \<1.0 ´ 109/L.
   • Aspartate transaminase (AST): >2.5 x the upper limit of normal (ULN).
   • Alanine transaminase (AST): > 2.5 x the ULN.
   • Total bilirubin: > 1.5 x the ULN.
   • Corrected serum calcium >14 mg/dL (3.5 mmol/L).
   • Calculated or measured creatinine clearance \<20 mL/minute
7. Known positive for HIV or active infectious hepatitis, type B or C.
8. Patient has ³Grade 2 peripheral neuropathy within 14 days before enrollment.
9. Known hypersensitivity to thalidomide.