cancer of plasma cells multiple myeolma
Conditions
Interventions
Treatment will be given in an outpatient treatment setting in cycles. Each
cycle is 28 days.
Arm A: Melflufen 40 mg will be administered as a 30-minutes intravenous
infusion on Day 1 of every 28-day
Sponsors
Oncopeptides AB
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, age 18 years or older 2. A prior diagnosis of multiple myeloma with documented disease progression requiring further treatment at time of screening 3. Measurable disease defined as any of the following: * Serum monoclonal protein >= 0.5 g/dL by protein electrophoresis. * >= 200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis * Serum free light chain >= 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio 4. Received 2-4 prior lines of therapy (Appendix D), including lenalidomide and a PI, either sequential or in the same line, and is refractory (relapsed and refractory or refractory) to both the last line of therapy and to lenalidomide (>= 10 mg) administered within 18 months prior to randomization. Refractory to lenalidomide is defined as progression while on lenalidomide therapy or within 60 days of last dose, following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per cycle. 5. Life expectancy of >= 6 months. 6. Eastern Cooperative Oncology Group (ECOG) performance status = 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days prior to first drug administration) * Platelet count >= 75,000 cells/mm3 (75 x 109/L) (without transfusions during the 10 days prior to first drug adminis
Exclusion criteria
Exclusion criteria: 1. Primary refractory disease (i.e. never responded (>= MR) to any prior therapy) 2. Evidence of mucosal or internal bleeding or platelet transfusion refractory (platelet count fails to increase by > 10,000 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 conduction system abnormalities, uncontrolled hypertension, >= grade 3 thromboembolic event in the last 6 months), 4. Prior exposure to pomalidomide 5. Known intolerance to IMiDs. (>= Grade 3 hypersensitivity reaction or at the investigators discretion) 6. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization. 7. Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cel carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance. 8. Pregnant or breast-feeding females 9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation 10. Known human immunodeficiency virus or active hepatitis C viral infection 11. Active hepatitis B viral infection (defined as HBsAg+). * Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-). * Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the discretion of the investigator after consideration of risk of reactivation. 12. Concurrent symptomatic amyloidosis or plasma cell leukemia. 13. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) 14. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to randomization. The use of live vaccines within 30 days before randomization. IMiDs, PIs or corticosteroids within 2 weeks prior to randomization. Other investigational therapies and monoclonal antibodies within 4 weeks of randomization. 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 randomization 15. Residual side effects to previous therapy > grade 1 prior to randomization (Alopecia any grade and/or neuropathy grade 2 without pain are permitted) 16. Prior peripheral stem cell transplant within 12 weeks of randomization 17. Prior allogeneic stem cell transplantation with active graft-versushost-disease). 18. Prior major surgical procedure or radiation therapy within 4 weeks of the randomization (this does not include limited course of radiation used for management of bone pain within 7 days of randomization). 19. Known intolerance to steroid therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint* * PFS | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary endpoints* * ORR * DOR * OS * Frequency and grade of Adverse Events (AE). Other Secondary Endpoints* * CBR * TTR * TTP * Duration of clinical benefit * Best response during the study (sCR, CR, VGPR, PR, MR, stable disease [SD] or PD) * Primary and secondary endpoints as assessed by investigators * PK parameters of melphalan * All tumor response and progression-dependent endpoints are as assessed by the IRC according to the IMWG-URC (Rajkumar et al. 2011, Appendix C) unless otherwise specified. Exploratory endpoints * PK parameters of melphalan, safety and efficacy variables specified in key secondary and other secondary endpoints * MRD in patients that achieve a CR • An additional Exploratory Endpoint has been added to describe the endpoints to evaluate the new study objective | — |
Countries
Netherlands
Outcome results
None listed