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.

Phase 1

• Conditions: Patients with Relapsed Refractory Multiple Myeloma who are Refractory to Pomalidomide and/or Daratumumab; MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000965-21-ES
• Lead Sponsor: Oncopeptides AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-11
• Last Update Posted: 31 October 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion 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. Measurable disease defined as any of the following:
? Serum monoclonal protein = 0.5 g/dL (= 5 g/L) by protein electrophoresis (SPEP)
? = 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
? Serum immunoglobulin free light chain =10 mg/dL (= 100 mg/L) AND 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. (Refractory status includes patients who relapse while on therapy or within 60 days of last dose).
5. Life expectancy of = 6 months.
6. ECOG performance status = 2. (Patients with worse performance status based solely on bone pain secondary to multiple myeloma will be eligible).
7. Female of child bearing potential (FCBP)* and non-vasectomized male agree to practice appropriate methods of birth control (See Section 7.6.1).
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 QTcF interval of = 470 msec (Appendix H).
10. The following laboratory results must be met during screening (within 21 days) and also prior to 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 before first drug administration)
? 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) or patients diagnosed with Gilberts syndrome, 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 = 45 mL/min. (Appendix G)
11. Must have, or accept to have, an acceptable central catheter for infusion of melflufen (Port a cath, PICC line, or central venous catheter).
*(FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory (i.e., unable to maintain a platelet count = 75,000 cells/mm3)
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. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction (MI), significant conduction system abnormalities, uncontrolled hypertension, = grade 3 thromboembolic event in the last 6 months).
3. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of treatment.
4. Primary refractory (never responded (= MR) to any prior 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.
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 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. IMiDs, PIs and or corticosteroids within 2 weeks prior to start of study treatment. Investigational therapies and monoclonal antibodies within 4 weeks of start of study 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 study treatment.
12. Residual side effects to previous therapy > grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy grade 2 without pain are permitted)
13. Prior autologous or allogeneic stem cell transplant within 12 weeks 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 4 weeks of the first dose of study treatment (this does not include limited course of radiation used for management of bone pain within 7 days of first dose of study therapy).
16. Known intolerance to steroid therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified