Melflufen with dexamethasone and continued daratumumab in patients with multiple myeloma

Phase 1

• Conditions: Multiple Myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-004349-35-DK
• Lead Sponsor: Klinisk Forskningsenhed, Medicinsk Afdeling, Hæmatologisk Afsnit, Sygehus Lillebælt, Vejle Sygehus

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-02-16
• Last Update Posted: 4 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

•Male or female, age 18 years or older;
•A prior diagnosis of multiple myeloma;
•Previously exposed to a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) and an immunomodulatory drug (thalidomide, lenalidomide or pomalidomide);
•Two to eight prior lines of therapy
•Refractory to daratumumab in the last line of therapy, defined as progressive disease
oduring treatment with daratumumab monotherapy or a daratumumab containing regimen, or
owithin 60 days of the last dose of daratumumab as monotherapy or part of a daratumumab containing regimen;
•Prior response to daratumumab, defined as at least minimal response achieved during daratumumab monotherapy or a daratumumab containing regimen;
•Measurable disease defined as any of the following:
oSerum monoclonal protein = 10 g/L by serum protein electrophoresis
o = 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
oSerum free light chain = 100 mg/L and abnormal serum kappa to lambda free light chain (FLC) ratio
•Life expectancy of = 6 months;
•ECOG performance status = 2. (Patients with performance status > 2 based solely on bone pain secondary to multiple myeloma may be eligible following approval of the sponsor);
•A negative serum or urine pregnancy test if the subject is a female of childbearing potential, defined as any sexually mature female who:
ohas not undergone a hysterectomy or bilateral oophorectomy and
ohas not been naturally postmenopausal for at least 24 consecutive months
?A sexually mature female who stopped having menstrual cycles due to cancer therapy cannot be considered naturally postmenopausal
•Patient agrees to practice appropriate methods of birth control;
•Ability to understand the purpose and risks of the study and provide signed and dated informed consent;
•Adequate organ function with the following laboratory results:
oAbsolute neutrophil count = 1,000 cells/mm3 (1.0 x 109/L)
oPlatelet count = 75,000 cells/ mm3 (75 x 109/L) (without transfusions required within 10 days prior to initiation of study treatment)
oHemoglobin = 5 mmol/l; red blood cell transfusions are permitted
oTotal Bilirubin = 1.5 x upper limit of normal, except patients diagnosed with Gilbert’s syndrome that have been approved by the sponsor
oAlanine transaminase = 3.0 x upper limit of normal
oRenal function: Estimated creatinine clearance by Cockcroft- Gault formula of = 45 mL/min and serum creatinine of = 175 µmol/l
•Patient must have or be willing to have an acceptable central catheter (port a cath, peripherally inserted central catheter, 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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

•Any somatic or psychiatric condition that in the investigator’s opinion would impose excessive risk to the patient or would adversely affect the patient’s participation in this study;
•Severe ongoing infection that in the investigator’s opinion would impose excessive risk to the patient
•Known intolerance to the required dose and schedule of study treatment;
•Evidence of platelet transfusion refractory thrombocytopenia (defined as platelet counts not increasing at least 10.000 cells/ mm3 [10 x 109/L] after a transfusion of an appropriate dose of platelets);
•Evidence of mucosal or internal bleeding that requires platelet transfusion within 10 days prior to initiation of study treatment;
•Pregnant or breast-feeding females;
•Known human immunodeficiency virus or active hepatitis B or C viral infection;
•The use of live vaccines within 30 days before initiation of study treatment;
•The use of any of the following therapies prior to initiation of study treatment in the time intervals specified below:
ocytotoxic agents within 3 weeks,
oproteasome inhibitors within 2 weeks,
oimmunomodulatory agents within 2 weeks,
omonoclonal antibodies other than daratumumab within 4 weeks
oCorsticosteroids more than a dosis equivalent to Prednisolone 10 mg per day (unless administered as part of a pre- or post-infusion schedule for daratumumab.) Corticosteroids up to an equivalent dose to Prednisolone 10 mg per day are allowed for symptom management of comorbid conditions, but dose should be stable for at least 7 days prior to initiation of therapy
oPeripheral stem cell transplant within 12 weeks prior to initiation of study treatment;
oother investigational therapies within five halflives of the involved drugs
•Prior allogeneic stem cell transplantation with active graft-versus-host-disease;
•= Grade 3 cardiac conduction system abnormalities unless patient has a pacemaker

Study & Design

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