Official Title
Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment
Phase
Phase 2Lead Sponsor
Hellenic Society of HematologyStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Multiple MyelomaIntervention/Treatment
DaratumumabStudy Participants
38This study will evaluate the effects of Daratumumab with dexamethasone in subjects with relapsed or refractory multiple myeloma and renal impairment.
This is a multicenter, single arm, open-label phase 2 study. Approximately 38 subjects will be enrolled to receive daratumumab + dexamethasone. Treatment cycles have duration of 28 days. Subjects will receive treatment until disease progression, death, unacceptable toxicity or for a maximum of 30 months. Drug administration and follow-up visits will occur more frequently for early cycles (weekly for the first 8 weeks, every two weeks for weeks 9-24 and then every 4 weeks). Disease evaluations will occur monthly and will involve mainly measurements of myeloma proteins. Other assessments may include bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin, and β2- microglobulin and albumin.
Daratumumab will be given at a dose of 16 mg/kg administered as an 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. Subjects will receive pre-infusion medications before infusions to mitigate potential IRRs Drug: Dexamethasone Dexamethasone will be administered at 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
Daratumumab at a dose of 16 mg/kg administered as an 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 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
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
