Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment (DARE)
Relapsed/Refractory Multiple Myeloma
About this trial
This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma focused on measuring Multiple Myeloma, MM, Relapsed, Refractory
Eligibility Criteria
Inclusion Criteria:
- Males and females at least 18 years of age.
- Voluntary written informed consent before performance of any study-related procedure.
Subject must have documented relapsed or refractory multiple myeloma as defined by the criteria below:
- Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma.
Measurable disease as defined by any of the following:
- Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL (except for IgA subtype: ≥ 0.5 g/dL) or urine M-protein level ≥ 200 mg/24 hours; or
- Light chain multiple myeloma: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free-light-chain ratio.
- Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide-based regimens.
- Documented evidence of progressive disease (PD) as defined by the IMWG 2014 on or after the last regimen if the patient responded to previous regimens.
- Renal impairment defined as eGFR < 30 ml/min/1.72 m2 (calculated with the CKD-EPI formula) or in need for dialysis
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
- Willingness and ability to participate in study procedures.
- Reproductive Status
Exclusion Criteria:
- Previous therapy with Daratumumab or other anti-CD38 therapy.
- Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1.
- Cumulative dose of corticosteroids greater than or equal to the equivalent of 140mg prednisone for ≥4 days or a dose of corticosteroids greater than or equal to the equivalent of 40 mg/day of dexamethasone for ≥4 days within the 2-week period prior to Cycle 1, Day 1.
- Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within 12 weeks before Cycle 1, Day 1.
- Clinical signs of meningeal involvement of multiple myeloma.
- Chronic obstructive pulmonary disease (COPD), persistent asthma, or a history of asthma within 5 years.
Clinically significant cardiac disease, including:
- Myocardial infarction within 1 year, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
- Cardiac arrhythmia (CTCAE Grade 2 or higher) or clinically significant ECG abnormalities.
- ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec.
- Known active hepatitis B, or C.
- Known HIV infection.
Prior or concurrent malignancy, except for the following:
- Adequately treated basal cell or squamous cell skin cancer.
- Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior to study entry.
Any of the following laboratory test results during Screening:
- Absolute neutrophil count ≤1.0 × 109/L;
- Hemoglobin level ≤7.5 g/dL (≤4.65 mmol/L);
- Platelet count <75 × 109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells and <50x109/L in patients in whom more than 50% of bone marrow nucleated cells are plasma cells;
- Alanine aminotransferase level ≥2.5 times the upper limit of normal (ULN);
- Pregnant or nursing women
Sites / Locations
- General Hospital of Athens "Alexandra"
Arms of the Study
Arm 1
Experimental
Single arm trial receiving daratumumab with dexamethasone (DaraD)
Daratumumab was given at a dose of 16 mg/kg administered as an intravenous (IV) infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Dexamethasone was administered according to the standard recommended dose of 40 mg (20 mg for patients > 75 years of age) orally once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle.