Nelfinavir and Lenalidomide/Dexamethasone in Patients With Progressive Multiple Myeloma That Have Failed Lenalidomide-containing Therapy

Inclusion Criteria:

• Patient must have given written informed consent (including the drug-specific informed consent for Revlimid) before registration.
• Multiple myeloma having progressed after at least two months of lenalidomide-containing therapy (progressive disease during treatment with lenalidomide or <60 days after such treatment).

• Measurable disease for myeloma defined as one of the following:

  1. Serum monoclonal protein (M-protein) ≥10 g/L IgG or ≥5 g/L IgA, IgM, IgD
  2. Urine M-protein ≥200 mg/24h
  3. To be considered only if patient has no evidence of measurable disease with one of the criteria above: serum free light chain (FLC) ratio of kappa/lambda either >1.65 or <0.26 (baseline level of involved FLC has to be ≥100 mg/L)
• Adverse events from previous treatment has recovered to grade ≤2.
• Age ≥18 years.
• WHO performance status 0-2.
• Adequate hematological values: neutrophils ≥1 x 109/L, platelets ≥75 x 109/L
• Adequate hepatic function: bilirubin ≤1.5 x ULN, AST and AP ≤2.5 x ULN
• Adequate renal function: calculated creatinine clearance >50 mL/min, according to the formula of Cockcroft-Gault
• Adequate cardiac function: EF ≥40% assessed by echocardiography or MUGA scan
• Negative HIV test.
• Women are not breastfeeding. Women of child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative serum pregnancy test (minimum sensitivity of 25 mIU/ml) before inclusion (within 7 days) into the trial is required for all women of child-bearing potential. Men agree not to father a child during participation in the trial and during 12 months thereafter.
• Patient compliance and geographic proximity allow proper staging and follow-up.

Exclusion Criteria:

• Previous malignancy within 2 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
• Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling patient diary, or interfering with compliance for oral drug intake.
• Concurrent treatment with other experimental drugs or other anti-cancer therapy (chemotherapeutical/biological agents, radiation therapy). Treatment in a clinical trial within 30 days prior to trial entry.
• Known hypersensitivity or uncontrolled side effects related to trial drug(s) or hypersensitivity to any other component of the trial drugs.
• Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information.
• Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).
• Unstable cardiovascular disease.
• Known or clinically suspected myeloma manifestations in the central nervous system.
• Previous grade 4 adverse events attributable to treatment with lenalidomide.
• Patients who are on strong CYP3A4 modulators that cannot be replaced at least one week before the first dose of trial drugs and for the period of the trial.