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
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Concentration unit: mg/ml milligram(s
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 relapsed and / or refractory multiple myeloma as defined by the criteria below: a)Measurable disease as defined by any of the following: oSerum 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 oLight chain multiple myeloma for patients without measurable disease in the serum or urine by SPEP/UPEP: Serum immunoglobulin free light chain = 10 mg/dL and abnormal serum immunoglobulin kappa lambda free-light-chain ratio. 4.Prior treatment with at least two lines of treatment including lenalidomide and a PI for MM (induction followed by any planned high dose therapy or consolidation or maintenance would be considered as one regimen). 5.Documented evidence of progressive disease (PD) as defined by the modified IMWG criteria on or after the last regimen. 6.Karnofsky Performance Status score of = 70. 7.All of the following laboratory test results during screening: •Absolute neutrophil count (ANC) of = 1.0 x 109/L. •Platelet count of = 75 x 109/L in patients in whom 7.5 g/dL •Alanine aminotransferase =65 years) no F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1.Patient has received any of the following therapies: •Radiotherapy or systemic therapy within 2 weeks of baseline. •Prior Allogeneic hematopoietic stem cell transplantation; or Autologous stem cell transplantation within 12 weeks of baseline. •Prior Treatment with any CD38-antibody (i.e. daratumumab, isatuximab). 2.Clinically significant cardiac disease, including: a)Myocardial infarction within 6 months, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV). b)Cardiac arrhythmia (CTCAE Grade 3 or higher) or clinically significant ECG abnormalities. c)ECG showing a baseline QT interval as corrected >470 msec. 3.Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. 4.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)Patient is 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). 5.Patient is known to be seropositive for human immunodeficiency virus (HIV) 6.Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to enrolment. 7.Hypersensitivity to the active substance or to any of the excipients. 8.Any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with subject’s ability to give informed consent, the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study. 9.Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate changes in bone resorption markers after 4 months of daratumumab monotherapy. Namely, C-telopeptide of collagen type 1 (CTX) and tartrate-resistant acid phosphatase-5b (TRACP-5b) will be evaluated at baseline and then every 2 months of therapy.;Secondary Objective: Secondary objectives are the following: Increases of serum markers of bone formation after 4, 8 and 12 months of daratumumab monotherapy (or at the end of therapy). Reductions of serum markers of bone resorption after 8 and 12 months of daratumumab monotherapy (or at the end of therapy). Reductions of circulating receptor activator of nuclear factor kappa-B ligand (RANKL), RANKL/ osteoprotegerin (OPG) ratio, C-C motif chemokine ligand 3 (CCL3), dickkopf-1 (Dkk1), sclerostin (SOST) and activin-A after 4, 8 and 12months of therapy (or at the end of therapy). Changes in Bone Mineral Density (BMD) of the lumbar spine measured after 6 and 12 months of therapy. The evaluation of the immunomodulatory effects of daratumumab on T cells. Progression Free Survival (PFS), Time to Next Treatment (TtNT) and Overall Survival (OS). Skeletal-related events (SRE); pathological fractures, need for radiotherapy or surgery to the bones, and spinal cord compression.;Primary end point(s): Change from baseline in bone resorption markers CTX and TRACP-5b after 4 months of daratumumab monotherapy;Timepoint(s) of evaluation of this end point: 4 months of daratumumab monotherapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: For the entire duration of the study.;Secondary end point(s): • Change from baseline in bone formation markers bALP, OC and PINP after 4, 8 and 12 months of daratumumab monotherapy (or at the end of therapy). • Change from baseline in bone resorption markers CTX and TRACP-5b after 8 and 12 months of daratumumab monotherapy (or at the end of therapy). • Change from baseline in RANKL, RANKL/OPG ratio, CCL3, Dkk1, SOST and activin-A after 4, 8 and 12months of daratumumab monotherapy (or at the end of therapy). • Change in Bone Mineral Density (BMD) of lumbar spine measured by DXA after 6 and 12 months of daratumumab monotherapy. • Immunomodulatory effects of daratumumab on T cells by comprehensive molecular and phenotypic studies and correlations with bone markers. • PFS, OS. • Time to next treatment. • Skeletal related events. • Safety (adverse events). | — |
Countries
Greece
Contacts
Public ContactHealth Data Specialists Ireland
Health Data Specialists Ireland Limited
Outcome results
None listed