Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE)

• Response rate [ Time Frame: Every 4 weeks untill progression ] [ Designated as safety issue: No ]
• Duration of Response [ Time Frame: Estimated average: 3 months. From the date of first documentation of response to the date of disease progression or death. ] [ Designated as safety issue: No ]
• Overall Survival [ Time Frame: Estimated average: 9 months. From randomization to the first evidence of progressive disease or death due to any cause ] [ Designated as safety issue: No ]
  Overal Survival (OS) is defined as the time from the date of randomization to the date of death or last contact

Study of Plitidepsin in combination with dexamethasone versus dexamethasone alone in patients with relapsed/refractory multiple myeloma.

Phase III Study in Patients with Relapsed/Refractory Multiple Myeloma to compare the efficacy of plitidepsin in combination with dexamethasone vs. dexamethasone alone measured by progression-free survival (PFS) and to evaluate tumor response, duration of response (DR) and overall survival (OS). The evaluation of efficacy after crossover from dexamethasone alone to plitidepsin and dexamethasone combination, of safety profile on both arms patients and of pharmacokinetics (PK) and pharmacokinetic /pharmacodynamic (PK/PD) relationship will be performed.

• Drug: plitidepsin + dexamethasone
  plitidepsin: powder and solvent for concentrate for solution for infusion. 2 mg vial + 4 ml ampoule. 5 mg/m2 intravenously (i.v.) over three hours on Day 1 and 15 every 4 weeks. dexamethasone: 4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks at least one hour before plitidepsin infusion.
  Other Name: APLIDIN (plitidepsin)
• Drug: dexamethasone
  4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.

• Experimental: Arm A
  plitidepsin + dexamethasone combination
  Intervention: Drug: plitidepsin + dexamethasone
• Active Comparator: Arm B
  dexamethasone single agent
  Intervention: Drug: dexamethasone

Inclusion Criteria:

• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
• Life expectancy ≥ 3 months.
• Patients previously diagnosed with multiple myeloma
• Patients must have relapsed or relapsed and refractory multiple myeloma (MM) after at least three but not more than six prior therapeutic regimens for MM, including induction therapy and stem cell transplant in candidate patients, which will be considered as only one regimen.
• Patients must have received previous bortezomib-containing and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)
• Women must have a negative serum pregnancy test
• Voluntarily signed and dated written informed consent

Exclusion Criteria:

• Concomitant diseases/conditions
• Women who are pregnant or breast feeding.
• Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against MM
• Known hypersensitivity to any involved study drug or any of its formulation components