Multiple Myeloma MedDRA version: 20.0 Level: PT Classification code 10035226 Term: Plasma cell myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: DARZALEX
Product Name: DARZALEX
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Concentration unit: mg/ml mi
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be at least 18 years of age 2. Written informed consent 3. Subjects must have had documented multiple myeloma requiring treatment as defined by the criteria below: Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma at some point in their disease history requiring treatment according diagnostic criteria (IMWG updated criteria 2014, Rajkumar et al. 2014) see appendix I With measurable disease at screening (serum M-protein > 500 mg/dl or urine M-protein > 200 mg/24h, in case of oligosecretory MM serum free light chain > 10 mg/dl and abnormal kappa/lambda free light chain ratio) 4. GFR =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Subject has received prior Daratumumab or other Anti-CD38 antibodies (previous treatment with Elotuzumab is allowed) 2. Evidence of intolerance to bortezomib or known allergies, hypersensitivity or intolerance to monoclonal antibodies 3. Subject has received anti-myeloma treatment within 2 weeks of Cycle 1, day 1. The only exception is emergency use of a short course of corticosteroids (equivalent of Dexamethasone 40 mg/day for a maximum of 4 days) before treatment. 4. Active graft-versus host disease under immunosuppressive treatment 5. Subject is a woman who is pregnant or breastfeeding 6. Prior invasive malignancy within 5 years before trial inclusion 7. Active, uncontrolled infection. 8. Subject has peripheral neuropathy = 3 or neuropathic pain Grade 2 or higher 9. Subject has either of the following: a. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is only required for subjects suspected of having COPD b. Known moderate or severe persistent asthma, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study). 10. Subject has clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry, unstable angina, cardiac insufficiency New York Heart Association (NYHA) Class III-IV or uncontrolled arrhythmia 11. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significant is defined by presence of serum M-protein ? 3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less (Kyle et al. 2003). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment and organ damage (Kyle et al., 2003, 2007). 12. Subject has a diagnosis of Waldenström’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions. 13. Subject has had radiation therapy within 14 days of treatment 14. Subject has had plasmapheresis within 14 days of treatment. Screening laboratory values have to be performed after end of plasmapheresis. 15. Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis B surface and core antigen (anti HBs and anti HBc respectively), or hepatitis C (anti-HCV antibody positive or HCV RNA quantitation positive). 16. Subject has had major surgery within 2 weeks before treatment und has not fully recovered from surgery, or has surgery panned during the time the subject is expected to participate in the study. 17. Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs 18. Subject has any concurrent medical or psychiatric condition or disease (eg. active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for the participating in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy (overall response rate, ORR according to IMWG recommendations) of the combination of Daratumumab, Bortezomib and Dexamethasone in subjects with relapsed and refractory MM and impaired renal function;Secondary Objective: Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Evaluate renal efficacy according to IMWG (Dimopoulos et al., 2010) history of renal impairment will be documented in the eCRF Evaluate safety and tolerability of DVd as assessed by the incidence of clinical and laboratory toxicities Evaluate pharmacokinetics (Serum concentration of Daratumumab) ;Primary end point(s): overall response rate;Timepoint(s) of evaluation of this end point: evaluation of response at each cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluate safety and tolerability as assessed by the incidence of clinical and laboratory toxicities Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Evaluate renal efficacy according to IMWG (Dimopoulos, MA et al. 2010) Evaluate pharmacokinetics (Serum concentration of Daratumumab) ;Timepoint(s) of evaluation of this end point: Evaluate safety and tolerability as assessed by the incidence of clinical and laboratory toxicities Evaluate progression-free survival (PFS) Evaluate overall survival (OS) Evaluate renal efficacy according to IMWG (Dimopoulos, MA et al. 2010) Evaluate pharmacokinetics (Serum concentration of Daratumumab) | — |
Countries
Germany, Greece
Contacts
Public ContactCoordinating Investigator
University Medical Center of Hamburg Eppendorf
Outcome results
None listed