The Combination of Lenalidomide and Dexamethasone With or Without Intensification by High-dose Melphalan in the Treatment of Multiple Myeloma

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form. 2. Age 60-75 years at the time of signing the informed consent form. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Symptomatic MM requiring therapy. 5. Measurable monoclonal protein in serum and/or urine 6. Monoclonal plasma cells in the bone marrow >/= 10% and/or biopsy-proven plasmacytoma 7. Myeloma-related organ dysfunction, at least one of [C] Calcium elevation in the serum (> 11.5 mg/dL or > 2.65 mmol/l) [R] Renal insufficiency (creatinine > 173 μmol/l or > 2 mg/dL) [A] Anemia (Hb < 10 g/dL or 2 g/dL < normal) [B] Bone lesions or general osteoporosis 8. ECOG PS of </= 2 ... 9. Laboratory test results within these ranges within 1 week prior to randomization:

• ANC >/= 1.0 x 109/L.
• Platelet count >/= 75 x 109/L or in case of bone marrow infiltration with myeloma cells >/= 30 x 109/L.
• Total bilirubin </= 2 mg/dL.

• AST (SGOT) and ALT (SGPT) </= 3 x ULN. 8. Female subjects of childbearing potential must: o Understand the study drug is expected to have a teratogenic risk

  o Agree to use, ..., effective contraception without interruption,...

  o Understand that even if she has amenorrhea, she must follow all the advice on effective contraception.

  o She understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy

  o Agree to have a medically supervised pregnancy test ...

• Male subjects must

  o Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study drug therapy ...

  • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.

• All subjects must

  • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.

  • Agree not to share study drug with another person and to return all unused study drug to the investigator.

    9. Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

    10. Able to receive antithrombotic prophylaxis (...). 11. Life-expectancy > 3 months.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF.
2. Pregnant or lactating females
3. Any condition, incl. 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. Patient currently is enrolled in another clinical research study or has been enrolled ...within 4 weeks before randomization and/or is receiving an investigational agent for any reason ...
5. Known hypersensitivity to thalidomide, dexamethasone, or melphalan.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of lenalidomide.
8. Concurrent use of other anti-cancer agents or treatments.
9. Known positive for HIV or active infectious hepatitis, type A, B or C or treponema pallidum
10. Prior treatment with dexamethasone discontinued because of ≥ grade 3 dexamethasone-related toxicity.
11. Any prior chemotherapy with the exception of a short course of dexamethasone more than 4 weeks before randomization.
12. Immunotherapy or antibody therapy within 8 weeks before randomization.
13. Major surgery within 4 weeks before randomization.
14. Renal failure requiring dialysis.
15. Myocardial infarction within 6 months before randomization, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
16. Severe pulmonary disease (diffusion capacity < 60% of normal).
17. Treatment for cancer other than MM within 5 years before randomization, with the exception of basal cell carcinoma or cervical cancer in situ.
18. Cardiac amyloidosis.
19. Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to the protocol.
20. Any systemic infection requiring treatment.

21. Unability or unwillingness of the patient to receive antithrombotic prophylaxis.

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