A PK, Safety and Tolerability Study of Peripheral and Central Infusion of Melflufen in RRMM Patients

Inclusion Criteria: 1. Male or female, age 18 years or older 2. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; 3. A prior diagnosis of multiple myeloma (MM) with documented disease progression in need of treatment at time of screening; 4. Measurable disease defined as any of the following: * Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) * ≥ 200 mg/24hr of monoclonal protein in the 24hour urine collection by electrophoresis (UPEP) * Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio 5. Received at least 2 prior lines of therapy and is refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI). The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10 and Appendix 8. 6. Adequate peripheral arm veins for repeated intravenous infusions 7. Life expectancy of ≥ 6 months; 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, see Appendix 6. Patients with ECOG performance status \> 2 solely based on bone pain secondary to MM may be eligible following consultation and approval of medical monitor; 9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec, see Appendix 11; 10. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study treatment administration on Cycle 1 Day 1: * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm³ (1.0 x 10⁹/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of study treatment) * Platelet count ≥ 75,000 cells/ mm³ (75 x 10⁹/L) (without transfusions during the 10 days prior to initiation of therapy) * Hemoglobin ≥ 8.0 g/dL (Red blood cell \[RBC\] transfusions are permitted) * Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), except patients diagnosed with Gilbert's syndrome that have been reviewed and approved by the Medical Monitor * Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x ULN * Renal function: Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula of ≥ 45 mL/min, see Appendix 12. 11. Must have or be willing to have an acceptable central catheter (Port a Cath, peripherally inserted central catheter \[PICC\] line, or central venous catheter \[CVC\]) and a PVC; 12. a) Male patients: A male patient is eligible if he agrees to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrains from donating sperm during this period b) Female patients: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: I. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 or II. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 28 days after the last dose of study treatment Exclusion Criteria: 1. Primary refractory disease (i.e. never responded with at least minimal response \[MR\] to any prior therapy); 2. Evidence of mucosal and/or internal bleeding or platelet transfusion refractory (platelet count fails to increase by \> 10,000 cells/mm³ after a transfusion of an appropriate dose of platelets); 3. 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. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant cardiac conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months); 4. Known active infection that is uncontrolled or has required intravenous systemic therapy within 14 days of randomization. Patients that have required oral anti-infective treatment within 14 days of randomization should be discussed with the Medical Monitor; 5. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance; 6. Pregnant or breast-feeding females; 7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation; 8. Human immunodeficiency virus (HIV) or active hepatitis B or C viral infection; 9. Concurrent known or suspected amyloidosis or plasma cell leukemia; 10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes); 11. Known central nervous system (CNS) or meningeal involvement of myeloma 12. Any of the following treatments, within the specified timeframe * Previous cytotoxic therapies, including cytotoxic investigational agents, for MM within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. * The use of live vaccines within 30 days before initiation of therapy. * IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. * Other investigational therapies and monoclonal antibodies within 4 weeks of initiation of therapy. * Prednisone up to but no more than 10 mg orally q.d. or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy. Other washout times may be considered following consultation with the medical monitor. 13. Residual side effects to previous therapy \> Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted); 14. Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy; 15. Prior allogeneic stem cell transplantation with active graft-versus-host-disease; 16. Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy); 17. Known intolerance to the required dose and schedule of steroid therapy, as determined by the investigator; 18. Known hypersensitivity reaction to melphalan, melflufen or its excipients 19. Prior treatment with melflufen