Patients with Relapsed Refractory Multiple Myeloma who are Refractory to Pomalidomide and/or Daratumumab 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 A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening. 3. Measurable disease defined as any of the following: ? Serum monoclonal protein = 0.5 g/dL (= 5 g/L) by protein electrophoresis (SPEP) ? = 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP) ? Serum immunoglobulin free light chain =10 mg/dL (= 100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio 4. A minimum of 2 prior lines of therapy, including an IMiD and a PI, and is refractory to pomalidomide and/or daratumumab. (Refractory status includes patients who relapse while on therapy or within 60 days of last dose). 5. Life expectancy of = 6 months. 6. ECOG performance status = 2. (Patients with worse performance status based solely on bone pain secondary to multiple myeloma will be eligible). 7. Female of child bearing potential (FCBP)* and non-vasectomized male agree to practice appropriate methods of birth control (See Section 7.6.1). 8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information. 9. 12-lead ECG with QTcF interval of = 470 msec (Appendix H). 10. The following laboratory results must be met during screening (within 21 days) and also prior to study drug 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 before first drug administration) ? Platelet count = 75,000 cells/mm3 (75 x 109/L) (without transfusions required during the 10 days prior to initiation of therapy) ? Hemoglobin = 8.0 g/dl (RBC transfusions are permitted) ? Total Bilirubin = 1.5 x upper limit of normal (ULN) or patients diagnosed with Gilberts syndrome, have been reviewed and approved by the medical monitor). ? AST (SGOT) and ALT (SGPT) = 3.0 x ULN ? Renal function: Estimated creatinine clearance by Cockcroft-Gault formula = 45 mL/min. (Appendix G) 11. Must have, or accept to have, an acceptable central catheter for infusion of melflufen (Port a cath, PICC line, or central venous catheter). *(FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory (i.e., unable to maintain a platelet count = 75,000 cells/mm3) 2. 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 (MI), significant conduction system abnormalities, uncontrolled hypertension, = grade 3 thromboembolic event in the last 6 months). 3. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of treatment. 4. Primary refractory (never responded (= MR) to any prior therapy) 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. 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. Known HIV or active hepatitis B or C viral infection 9. Concurrent symptomatic amyloidosis or plasma cell leukemia 10. POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes] 11. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. IMiDs, PIs and or corticosteroids within 2 weeks prior to start of study treatment. Investigational therapies and monoclonal antibodies within 4 weeks of start of study 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 study treatment. 12. Residual side effects to previous therapy > grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy grade 2 without pain are permitted) 13. Prior autologous or allogeneic stem cell transplant within 12 weeks of initiation of therapy 14. Prior allogeneic stem cell transplant with active graft-versus-host- disease (GVHD). 15. Prior major surgical procedure or radiation therapy within 4 weeks of the first dose of study treatment (this does not include limited course of radiation used for management of bone pain within 7 days of first dose of study therapy). 16. Known intolerance to steroid therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess overall response rate (ORR), i.e. proportion of patients with = Partial response (PR) [stringent CR (sCR), complete response (CR), very good partial response (VGPR), and PR] as best response in efficacy evaluable patients according to IMWG Uniform Response Criteria , for the pomalidomide and daratumumab refractory groups separately.;Secondary Objective: Key Secondary Objectives - To assess PFS according to IMWG Criteria - To assess duration of response (DOR) in efficacy evaluable patients with = PR (sCR, CR, VGPR, PR) as best response according to IMWG Uniform Response Criteria - To assess Overall Survival (OS) Other Secondary Objectives - To assess clinical benefit rate (CBR, i.e. proportion of patients with = MR) as best response in efficacy evaluable patients, time to response (TTR), time to progression (TTP) - To assess the safety and tolerability;Primary end point(s): ORR (Overall Response Rate);Timepoint(s) of evaluation of this end point: During the course of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PFS - DOR - OS - CBR - Time to response (TTR) - Time to progression (TTP) - Duration of SD - Frequency and grade of AEs;Timepoint(s) of evaluation of this end point: During the course of the study | — |
Countries
Italy, Spain, United States
Contacts
Public ContactClinical Operations Director
Oncopeptides AB
Outcome results
None listed