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

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