Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients
Relapsed and/or Relapsed-refractory Multiple Myeloma
About this trial
This is an interventional treatment trial for Relapsed and/or Relapsed-refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Male or female, age 18 years or older
- Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
Patient has measurable disease defined as any of the following:
- Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
- ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
- Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- If no monoclonal protein is detected, then ≥ 30% monoclonal bone marrow plasma cells
- Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
- Life expectancy of ≥6 months
- Patient has an ECOG performance status ≤ 2 (Patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible)
- Females of childbearing potential must have a negative serum or urine pregnancy test prior to patient registration
- Female patients of child bearing potential and non-vasectomized male patients agree to practice appropriate methods of birth control
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
- The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen
- 12 lead ECG with QtcF interval ≤ 470 msec
The following laboratory results must be met within 21 days of patient registration:
- Absolute neutrophil count ≥ 1,000 cells/dL (1.0 x 109/L)
- Platelet count ≥ 75,000 cells/dL (75 x 109/L)
- Hemoglobin ≥ 8.0 g/dL
- Total Bilirubin ≤ 1.5 x upper limit of normal
- Renal function: Estimated creatinine clearance ≥ 45 ml/min or serum creatinine ≤ 2.5 mg/dL
- AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
Exclusion Criteria:
- Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
- Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participation in this study
- Known active infection requiring parenteral or oral anti-infective treatment
- Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix
- Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration.
- Pregnant or breast-feeding females
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
- Known HIV or hepatitis B or C viral infection
- Patient has concurrent symptomatic amyloidosis or plasma cell leukemia
- POEMS syndrome
- Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. Biologic, novel therapy (including investigational agents in this class) or corticosteroids within 2 weeks prior to patient registration. Patient has side effects of the previous therapy > grade 1 or previous baseline.
- Prior peripheral stem cell transplant within 12 weeks of patient registration
- Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
- Known intolerance to steroid therapy
Sites / Locations
- Dana Farber Cancer Institute
- Karmanos Cancer Center
- Universtity of North Carolina
- Vejle Hospital
- Turin Hospital Myeloma Unit
- Erasmus University Medical Center
- Sahlgrenska Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Phase I: Melflufen 15 mg + Dexamethasone
Phase I: Melflufen 25 mg + Dexamethasone
Phase I: Melflufen 40 mg + Dexamethasone
Phase I: Melflufen 55 mg + Dexamethasone
Phase I + II: Melflufen 40 mg + Dexamethasone
Phase II: Melflufen 40 mg (Single Agent)
Intravenous (IV) infusion of 15 milligram (mg) melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
IV infusion of 25 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
IV infusion of 40 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
IV infusion of 55 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
IV infusion of 40 mg melflufen on Day 1 of each 21-day or 28-day treatment cycles, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycles. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each treatment cycle.
IV infusion of 40 mg melflufen on Day 1 of each 28-day treatment cycle.