Protocol Summary

Protocol No.: OCR15175

Sponsor Protocol No.: OP-106

Study Title
A Single Arm, Open-Label, Phase 2 Study of Melflufen in Combination with Dexamethasone in Patients with Relapsed Refractory Multiple Myeloma who are Refractory to Pomalidomide and/or Daratumumab

Principal Investigator(s)
Moreb, Jan

Objective
This study will evaluate melflufen in combination with dexamethasone in the treatment of relapsed refractory multiple myeloma in adult patients with disease refractory to pomalidomide and/or daratumumab. All patients in the study will be treated with melflufen on Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.

Description
Melflufen is designed for targeted delivery of alkylating moieties to tumor cells. In contrast to other alkylating agents that are hydrophilic, the lipophilicity of melflufen leads to rapid and extensive distribution into tissues and cells. Inside cells, melflufen may directly bind DNA or is readily metabolized by intracellular peptidases into the well-known antitumor compound melphalan, or by esterases into des-ethylmelflufen, which also has alkylating properties. Due to the high activity of peptidases and esterases in human tumor cells, the formation of melflufen's metabolites is rapid in these cells with subsequent inflow of more melflufen. Since des-ethylmelflufen and melphalan are relatively hydrophilic, there is a possibility for intracellular trapping of these alkylators.

Phase: Phase II

Age Group: Adult

Scope: National

Treatment
Melflufen + dexamethasone:
Melflufen 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

Detailed Eligibility
INCLUSION CRITERIA:
1. Age 18 years or older
2. A prior diagnosis of multiple myeloma with documented disease progression
3. Measurable disease based on either of a) serum monoclonal protein by protein electrophoresis (SPEP), b) monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP), and/or c) serum immunoglobulin free light chain combined with 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
5. Life expectancy of ≥ 6 months
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Female of child bearing potential (FCBP) and non-vasectomized male agree 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 and authorization to use protected health information
9. 12-lead ECG with QTc interval within defined limit
10. Acceptable laboratory results during screening and prior to first study drug administration of the following parameters: absolute neutrophil count (ANC), platelet count, hemoglobin, total bilirubin, aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT), renal function based on estimated creatinine clearance
11. Must have, or accept to have, an acceptable central catheter for infusion of melflufen

EXCLUSION CRITERIA:
1. 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 participating in this study
3. Known active infection requiring parenteral or oral anti-infective treatment within defined period
4. Primary refractory disease
5. Other malignancy diagnosed or requiring treatment within the defined period with specific exceptions
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 defined values prior to start of study treatment
12. Residual side effects to previous therapy over specific grade prior to initiation of therapy
13. Prior autologous or allogeneic stem cell transplant within defined period 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 specified period of the first dose of study treatment (with defined exception).
16. Known intolerance to steroid therapy

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UF Gainesville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02963493