Patients with relapsed and refractory multiple myeloma. MedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851
Conditions
Sponsors
Oncopeptides AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, age 18 years or older; 2. Capable of giving signed informed consent 3. A prior diagnosis of 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 IMiD and a PI. The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy; 6. Adequate peripheral arm veins for repeated intravenous infusions 7. Life expectancy of = 6 months; 8. Eastern Cooperative Oncology Group (ECOG) performance status = 2; 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; 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 • AST (SGOT) and ALT (SGPT) = 3.0 x ULN • Renal function: Estimated glomerular filtration rate (eGFR) by CKD-EPI formula of = 45 mL/min; 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 the protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrain 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) or ii. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days after the last dose of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. Primary refractory disease (i.e. never responded with at least 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate and compare the PK variables Cmax, AUC(0-t) and AUC(0-8) of desethylmelflufen and elimination half-life (t½) for melflufen, melphalan and desethylmelflufen after central and peripheral intravenous infusion of melflufen. - To assess safety and general tolerability of melflufen - To evaluate efficacy: • Best response during the study • Overall response rate (ORR) • Clinical benefit rate (CBR) • Duration of response (DOR) • Duration of Clinical Benefit (DOCB) • Time to response (TTR) • Time to progression (TTP) • Time to next treatment (TTNT) • Progression Free Survival (PFS) ;Primary end point(s): • Maximum observed concentration (Cmax) • Area under the concentration-time profile from 0 hours to end of drug infusion (AUC(0-t)) • Area under the concentration-time profile from 0 hours to infinity (AUC(0-8)) • Frequency and Grade of local reactions including phlebitis at infusion site after peripheral intravenous administration. ;Main Objective: - To evaluate and compare the pharmacokinetic (PK) variables Cmax, AUC(0-t) and AUC(0-8) of melflufen and melphalan after central and peripheral intravenous infusion of melflufen. - To assess the local tolerability of peripheral intravenous administration of melflufen;Timepoint(s) of evaluation of this end point: During the course of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Cmax • AUC(0-t) • AUC(0-8) • Elimination half-life t½ • Frequency and Grade of Treatment Emergent Adverse Events (TEAEs) • Best Response (stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) or progressive disease (PD) • ORR (including CR/sCR, VGPR and PR) • CBR proportion of patients with = MR as best response • DOR (time from the first confirmed response of sCR, CR, VGPR or PR to first confirmed disease progression, or death due to any cause. • DOCB (time from first evidence of confirmed assessment of sCR, CR, VGPR, PR, or MR to first confirmed disease progression, or to death due to any cause.) • TTR (time from randomization to the date of the first documented confirmed response in a patient that has responded with = PR (sCR, CR, VCPR or PR)) • TTP (time from the date of randomization to the date of the first documented confirmed PD) • TTNT (time from randomization to the date of next anti-myeloma treatment) • PFS (time from the date of randomization to the date of first documentation of confirmed PD or death due to any cause). ;Timepoint(s) of evaluation of this end point: During the course of the study | — |
Countries
Bulgaria, Czech Republic, Hungary, Ukraine, United States
Contacts
Public ContactClinical Trials Information Desk
Oncopeptides AB
Outcome results
None listed