Study of Daratumumab in combination with Bortezomib (VELCADE), Thalidomide, and Dexamethasone (VTD) in the first Line treatment of transplant eligible subjects with newly diagnosed Multiple Myeloma
- to determine if the addition of daratumumab to VTD will increase the proportion of subjects achieving stringent complete response (sCR) post completion of consolidation therapy compared with VTD alone.
- to determine if the use of daratumumab as single agent in maintenance compared to observation only will increase progression-free survival (PFS) when used after autologous stem cell transplant and consolidation therapy.
- to determine if the addition of daratumumab to VTD will improve:
o Progression-free survival (PFS) from first randomization
o Time to progression (TTP) from first randomization
o Complete response (CR) rate by the end of ASCT/consolidation
o Minimal residual disease (MRD) negative rate by the end of ASCT/consolidation
o Post-induction stringent complete response (sCR) rate
o Progression-free survival after next line of therapy (PFS2)
o Post-induction overall response rate (ORR) and rate of very good partial response (VGPR) or better
o Overall survival (OS)
o Duration of CR and sCR
- to determine if the addition of daratumumab to VTD will improve the assessment during maintenance of:
o Time to progression
o CR rate
o MRD negative rate
o PFS2
o Rate of improved response
o Rate of MRD negative conversion
o ORR
o OS
- To evaluate quality of life and health economic/resource utilization
- To assess immunogenicity of daratumumab
- To assess safety and tolerability of daratumumab in combination with VTD
- To evaluate daratumumab’s impact on response and resistance to treatment
- Subject must be between 18 and 65 years of age.
- Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease as defined by :
o Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma AND any one or more of the following myeloma defining events:
o Measurable disease as defined by any of the following:
- Newly diagnosed subjects eligible for high dose therapy and autologous stem cell transplantation.
- Subject must have an ECOG performance status score of 0, 1, or 2.
- Subject must have pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
o Hemoglobin ≥7.5 g/dL (≥5 mmol/L; prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted);
o Absolute neutrophil count (ANC) ≥1.0 x 109/L (GCSF use is permitted);
o AST ≤2.5 x upper limit of normal (ULN);
o ALT ≤2.5 x ULN;
o Total bilirubin ≤1.5 x ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, direct bilirubin ≤1.5 x ULN);
o Calculated creatinine clearance ≥40 mL/min/1.73 m2;
o Corrected serum calcium ≤14 mg/dL (<3.5 mmol/L); or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L);
o Platelet count ≥70 x 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50x109/L (transfusions are not permitted to achieve this minimum platelet count).
- Women who are partners of men and of childbearing potential must be practicing one of the following methods of birth control: subcutaneous hormonal implant, levonorgestrel-releasing intra-uterine system, medroxyprogesterone acetate depot, tubal sterilization, ovulation inhibitory progesterone only pills, or sexual intercourse with a vasectomized male partner (vasectomy must be confirmed by 2 negative semen analyses). Or women will commit to absolute and continuous abstinence confirmed to her physician on a monthly basis. Contraception will start 4 weeks before the start of therapy, during therapy including dose interruptions, for 4 weeks after discontinuation of thalidomide and for 4 months after discontinuation of daratumumab.
- A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing.
- Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
- Subject has received daratumumab or other anti-CD38 therapies previously.
- Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions,anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage.
- Subject has a diagnosis of Waldenström’s macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- Subject has prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
- Subject has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.
- Subject has had any prior or concurrent invasive malignancy (other than multiple myeloma) within 10 years of study start except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate adenocarcinoma diagnosed ≥3 years and without evidence of biochemical failure, or other cancer for which the subject has undergone potentially curative therapy and has no evidence of that disease for ≥10 years.
- Subject has had radiation therapy within 14 days of randomization.
- Subject has had plasmapheresis within 28 days of randomization.
- Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
- Subject has known chronic obstructive pulmonary disease (COPD) with an Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
- Subject has known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
- Subject is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have active hepatitis B or hepatitis C.
- 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 participating in this study.
Centre Hospitalier du Luxembourg (CHL)
Gloria MONTANES
gloria.montanes@lih.lu
+352 26 970 757
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This page provides the list of clinical studies currently registered in the LuxCLIN platform in the different therapeutic areas. By clicking on each study title, more information is displayed concerning the study objective and the participation conditions.
