It is an early clinical trial to assess a new drug (Melflufen) when given together with a steroid (Dexamethasone) and an approved drug (either Bortezomib or Daratumumab) in the treatment of patients with the cancer (MM) which returns after treatment and is not responded to treatment
- Conditions
- Patients with Relapsed or Relapsed-Refractory Multiple MyelomaMedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002120-24-CZ
- Lead Sponsor
- Oncopeptides AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 80
Patients will be considered eligible for inclusion in this study if they meet all of the following 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. One to four prior lines of therapy (Appendix D)
4. Measurable disease defined as any of the following:
•Serum monoclonal protein = 0.5g/dL by serum protein electrophoresis (SPEP)
• = 200 mg of monoclonal protein in the urine on 24-hour electrophoresis (UPEP)
•Serum free light chain (SFLC) = 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio
5. Life expectancy of = 6 months
6. ECOG performance status = 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor);
7. Patient is a female of childbearing potential (FCBP)* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, is a female not of child bearing potential, or is a male patient and agrees to practice appropriate methods of birth control.
8. Ability to understand the purpose and risks of the study and provide signed and dated informed consent;
9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of = 470 msec (Appendix H);
10. Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before 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 (14 days for pegfilgrastim) prior to initiation of therapy)
•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), 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 creatinine clearance by Cockcroft- Gault formula of = 45 mL/min and serum creatinine = 2.0 mg/dL(Appendix G);
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).
Regimen Specific
Regimen A - Melflufen + Bortezomib and Dexamethasone
A1 Must be intolerant or refractory to a prior IMiD; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose.
Regimen B - Melfufen + Daratumumab and Dexamethasone
B1 Must have had a prior IMiD and proteasome inhibitor (PI); alone or in combination and must be refractory or intolerant to an IMiD, PI or both.
*(FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been natura
Patients will be ineligible for this study if they meet any one of the following criteria:
1. Primary refractory disease (i.e. never responded with = 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 cardiac history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension = Grade 3 thromboembolic event in the last 6 months);
4. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of 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 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.Known human immunodeficiency virus or active hepatitis B or C viral infection (see criterion B5 for additional requirements for Regimen B);
9.Concurrent symptomatic amyloidosis or plasma cell leukemia;
10.POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
11.Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma 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 mAb 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;
12.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);
13.Prior peripheral stem cell transplant within 12 weeks of initiation of therapy;
14.Prior allogeneic stem cell transplantation with active graft-versus-host-disease);
15.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);
16. Known intolerance to the required dose and schedule of steroid therapy, as determined by the investigator.
Regimen specific exclusion criteria
Regimen A – Melflufen + Bortezomib and Dexamethasone
A1Refractory to a PI; refractory defined as failure to respond (MR or better) or progression while on therapy or withi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method