Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients

An Open-Label Phase I/IIa Study of the Safety and Efficacy of Melphalan-flufenamide (Melflufen) and Dexamethasone Combination for Patients With Relapsed and/or Relapsed-Refractory Multiple Myeloma

The study will explore escalating doses of melflufen in combination with dexamethasone in small groups of patients to find the maximum tolerated dose of melflufen. That dose will then be used to determine the efficacy and safety profile of melflufen in combination with dexamethasone in a larger group of patients.

Inclusion Criteria:

1. Male or female, age 18 years or older

2. Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease

3. Patient has measurable disease defined as any of the following:

   1. Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
   2. ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
   3. Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
   4. If no monoclonal protein is detected, then ≥ 30% monoclonal bone marrow plasma cells

4. 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

5. Life expectancy of ≥6 months

6. Patient has an ECOG performance status ≤ 2 (Patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible)

7. Females of childbearing potential must have a negative serum or urine pregnancy test prior to patient registration

8. Female patients of child bearing potential and non-vasectomized male patients agree to practice appropriate methods of birth control

9. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

10. The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen

11. 12 lead ECG with QtcF interval ≤ 470 msec

12. 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:

1. Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
2. 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
3. Known active infection requiring parenteral or oral anti-infective treatment
4. 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
5. 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.
6. Pregnant or breast-feeding females
7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
8. Known HIV or hepatitis B or C viral infection
9. Patient has concurrent symptomatic amyloidosis or plasma cell leukemia
10. POEMS syndrome
11. 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.
12. Prior peripheral stem cell transplant within 12 weeks of patient registration
13. 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
14. Known intolerance to steroid therapy