A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Melphalan flufenamide (Melflufen); Dexamethasone
Intervention description: IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.
Intervention MeSH terms: Dexamethasone; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 157.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: relapsed refractory multiple myeloma

Summary:

      This study will evaluate melflufen in combination with dexamethasone in adult patients with
      relapsed or refractory multiple myeloma in whose disease is refractory to pomalidomide and/or
      an anti-CD38 monoclonal antibody. All patients in the study will be treated with melflufen on
      Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, age 18 years or older

          -  A prior diagnosis of multiple myeloma with documented disease progression

          -  Measurable disease based on either of a) serum monoclonal protein by protein
             electrophoresis (SPEP), b) monoclonal protein in the urine on 24-hour urine
             electrophoresis (UPEP), and/or c) serum immunoglobulin free light chain combined with
             abnormal serum immunoglobulin kappa to lambda free light chain ratio

          -  A minimum of 2 prior lines of therapy including an IMiD and a PI and is refractory to
             pomalidomide and/or daratumumab

          -  Life expectancy of ≥ 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Female of child bearing potential (FCBP) and non-vasectomized male agree to practice
             appropriate methods of birth control

          -  Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information

          -  12-lead ECG with QTc interval within defined limit

          -  Acceptable laboratory results during screening and prior to first study drug
             administration of the following parameters: absolute neutrophil count (ANC), platelet
             count, hemoglobin, total bilirubin, aspartate transaminase (AST/SGOT) and alanine
             transaminase (ALT/SGPT), renal function based on estimated creatinine clearance

          -  Must have, or accept to have, an acceptable central catheter for infusion of melflufen

        Exclusion Criteria:

          -  Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory

          -  Any medical conditions that, in the Investigator's opinion, would impose excessive
             risk to the patient or would adversely affect his/her participating in this study

          -  Known active infection requiring parenteral or oral anti-infective treatment within
             defined period

          -  Primary refractory disease

          -  Other malignancy diagnosed or requiring treatment within the defined period with
             specific exceptions

          -  Pregnant or breast-feeding females

          -  Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
             confuse compliance or follow-up evaluation

          -  Known HIV or active hepatitis B or C viral infection

          -  Concurrent symptomatic amyloidosis or plasma cell leukemia

          -  POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein (M-protein) and skin changes]

          -  Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple
             myeloma within defined values prior to start of study treatment

          -  Residual side effects to previous therapy over specific grade prior to initiation of
             therapy

          -  Prior autologous or allogeneic stem cell transplant within defined period of
             initiation of therapy

          -  Prior allogeneic stem cell transplant with active graft-versus-host- disease (GVHD).

          -  Prior major surgical procedure or radiation therapy within specified period of the
             first dose of study treatment (with defined exception).

          -  Known intolerance to steroid therapy