Relapsed and /or Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: DARZALEX
Product Name: Daratumumab
Product Code: Daratumumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Concentrati
Sponsors
Hellenic Society of Hematology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Males and females at least 18 years of age. 2.Voluntary written informed consent before performance of any study-related procedure. 3.Subject must have documented multiple myeloma as defined by the criteria below: Monoclonal plasma cells in the bone marrow = 10% or presence of a biopsy proven plasmacytoma. AND any or more of the following myeloma defining events: •Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: • Hypercalcaemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) • Renal insufficiency: creatinine clearance 177 µmol/L (>2 mg/dL) • Anaemia: haemoglobin value of >20 g/L below the lower limit of normal, or a haemoglobin value 1 focal lesions on MRI studies 4.Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide-based regimens. 5.Documented evidence of progressive disease (PD) as defined by the modified IMWG criteria (see Appendix 4) on or after the last regimen if the patient responded to previous regimens. 6.Subjects must have 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 (100 mg/L) and abnormal serum immunoglobulin kappa lambda free-light-chain ratio. 7.Renal impairment defined as eGFR < 30 ml/min/1.73 m2 (calculated with the CKD-EPI formula, see section 7.1.1.9) or in need for dialysis. Patients who undergo intraperitoneal dialysis may also be included. 8.Eastern Cooperative Oncology Group (ECOG) performance status score of = 2. 9.Willingness and ability to participate in study procedures. 10.Reproductive Status a)Women of childbearing potential (WOCBP) must have two negative serum or urine pregnancy tests, one 10-14 days prior to start of the study drug and one within 24 hours prior to the start of study drug. Females are not of reproductive potential if they have been in natural menopause for at least 24 consecutive months, or have had a hysterectomy and/or bilateral oophorectomy. b)Women must not be breastfeeding. c)WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for 3 months after cessation of study treatment. d)Males who are sexually active must always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy. They must also agree to follow instructions for methods of contraception for 4 weeks before the start of treatment with study drugs, for the duration of treatment with study drugs, and for a total of 90 days post-treatment completion. on. The additional contraception of female partners of childbearing potential should also be considered. e)Male patients must not donate sperm for up to 90 days post treatment completion. f)Female patients must not donate eggs for up to 90 days post treatment c
Exclusion criteria
Exclusion criteria: 1.Previous therapy with daratumumab or other anti-CD38 therapy. 2.Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1. 3.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. 4.Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within 12 weeks before Cycle 1, Day 1. 5.Clinical signs of meningeal involvement of multiple myeloma. 6.Subject has either of the following: a.Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) 470 msec. 8.Any of the following: a. Known active hepatitis A b. Patient is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. c. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy). 9.Known to be seropositive for human immunodeficiency virus (HIV). 10.Amyloidosis, or any prior or concurrent malignancy, except for the following: a)Adequately treated basal cell or squamous cell skin cancer. b)Any cancer (other than in-situ) from which the subject has been disease-free for 3 years prior to study entry. 11.Any of the following laboratory test results during Screening: a)Absolute neutrophil count = 1.0 × 109/L; b)Hemoglobin level = 7.5 g/dL (= 4.65 mmol/L); c)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; d)Alanine aminotransferase level = 2.5 times the upper limit of normal (ULN); 12.Pregnant or nursing women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The Secondary objectives of the study are the following: To evaluate Overall Response Rates (ORR) To evaluate Renal Response Rates (RRR) To evaluate duration of response in patients (DoR) with RI. To evaluate time to next therapy (TNT). To evaluate Overall Survival (OS). To assess the safety and tolerability of Daratumumab with dexamethasone in patients with RRMM and RI.;Main Objective: The primary objective of this study is to evaluate progression free survival (PFS) in subjects with relapsed or refractory multiple myeloma and renal impairment treated with daratumumab and dexamethasone.;Primary end point(s): The primary endpoint of this study is Progression-free survival;Timepoint(s) of evaluation of this end point: The whole duration of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are the following: - Overall response rate - Renal Response rate - Duration of response - Time to next therapy - Overall survival - Safety (adverse events);Timepoint(s) of evaluation of this end point: The whole duration of the study | — |
Countries
Greece
Contacts
Public ContactHealth Data Specialists Ireland
Health Data Specialists Ireland Limited
Outcome results
None listed