Multicenter study to assess Pharmacokinetics of Melphalan During Treatment with Melflufen and Dexamethasone

Phase 1

Conditions: Patients with Relapsed Refractory Multiple and Impaired Renal Function
MedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-000478-31-CZ

Lead Sponsor: Oncopeptides AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 25

Inclusion Criteria

1. Male or female, age 18 years or older, at the time of signing the informed consent;
2. A prior diagnosis of MM with documented disease progression in need of treatment at time of screening;
3. Received 2- 4 prior lines of therapy.
4. Measurable disease defined as any of the following:
a. Serum monoclonal protein = 0.5 g/dL by serum protein electrophoresis (SPEP)
b. = 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
c. SFLC = 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio;
5. Life expectancy of = 6 months;
6. ECOG performance status = 2. (Patients with lower performance status based solely on bone pain secondary to MM 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, or the patient is male and agrees to practice appropriate methods of birth control (Section 7.1);
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 ;
10. Renal function: Estimated GFR by CKD-EPI formula on 2 consecutive screening evaluations. Patients meeting criteria for Screening 1, must also meet criteria for Screening 2 following optimal hydration (as determined by the investigator). Screening 2 must be on or as close as possible to treatment start date (preferably < 24-48 hours) but cannot exceed 72 hours.
Cohort 1 (a and b):
Screening 1: eGFR between =25mL/min to <45 mL/min
Screening 2: eGFR between =30 mL/min to <45 mL/min.
Cohort 2 will only be enrolled following approval from the
DSMC.
Cohort 2:
Screening 1: eGFR between = 15 mL/min to < 25 mL/min.
Screening 2: eGFR between =15 mL/min to < 30 mL/min.
Patients meeting Cohort 2, Screening 1 criteria that improve following hydration and meet Cohort 1, Screening 2 criteria may enroll in Cohort 1
Patients with fluctuating values of eGFR may be eligible following consideration of additional assessments in consultation with the medical monitor.
11. The following laboratory results must be met 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 required transfusions during the 10 days prior to initiation of therapy)
• Hemoglobin = 8.0 g/dl (red blood cell [RBC] transfusions are permitted)
• Total Bilirubin = 1.5 x upper limit of normal (ULN), or higher in patients diagnosed with Gilbert’s syndrome, that have been reviewed and approved by the medical monitor
• Aspartate transaminase / Serum glutamic oxaloacetic transaminase (AST /SGOT) and alanine transaminase / Serum glutamic pyruvic transaminase (ALT/ SGPT) = 3.0 x ULN;
12. Must have, or be willing to have, an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter);

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 10
F.1.3 Elderly (>=65 years) yes

Exclusion Criteria

1. Primary refractory disease (i.e. never responded with = MR to any prior therapy);
2. Evidence of mucosal or internal bleeding and/or are platelet transfusion refraktory (platelet count fails to increase by > 10,000 cells/mm3 [10.0 x 109/L] after 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 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;
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 MM 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 monoclonal antibodies (mAb) within 4 weeks of initiation of therapy. Prednisone up to but no more than 10 mg orally once daily (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 2 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 initiation of study therapy this does not include limited course of radiation used for management of bone pain to be completed within 7 days of initiation of study therapy. Plasmapheresis is not permitted within 14 days of initiation of therapy;
16. Known intolerance to steroid therapy;
17. Prior renal transplant;
18. Currently in need of renal dialysis.

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

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