A Clinical Study to Compare Daratumumab, VELCADE (bortezomib), Lenalidomide, and Dexamethasone (D-VRd) with VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects with Untreated Bone Marrow Cancer and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001545-13-CZ
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
1.Newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation due to:
?Being age =65years,or
?age 18-65years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with SCT or who refuse high-dose chemotherapy with SCT as initial treatment
2.Diagnosis of multiple myeloma as documented per International Myeloma Working Group Criteria:Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium,renal,anemia,bone(CRAB)criteria or biomarkers of malignancy criteria:
CRAB criteria:
1.Hypercalcemia:serum calcium >0.25mmol/L (>1mg/dL) higher than upper limit of normal (ULN) or >2.75mmol/L (>11mg/dL)
2.Renal insufficiency:creatinine clearance <40mL/min or serum creatinine >177 µmol/L (>2mg/dL)
3.Anemia:hemoglobin >2g/dL below the lower limit of normal or hemoglobin <10g/dL
Please see the complete list of criteria 2 in the Protocol Am on pg.38 and 39.
3.Must have measurable disease,as assessed by central laboratory,defined by any of the following:
- IgG,IgA,IgM,IgD,or IgE multiple myeloma:Serum monoclonal paraprotein (M-protein) level =1.0g/dL or urine M-protein level =200mg/24 hours;or
- Light chain multiple myeloma without measurable disease in serum or urine:Serum Ig FLC =10mg/dL and abnormal serum Ig kappa lambda FLC ratio
4.Eastern cooperative oncology group(ECOG) performance status score of 0,1 or2
5.Clinical laboratory values meeting the following criteria during the Screening Phase:
a.hemoglobin = 7.5 g/dL (= 5 mmol/L) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
b.absolute neutrophil count (ANC) = 1.0 x 109/L (granulocyte colony stimulating factor [G-CSF] use is permitted)
c.platelet count = 70x109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50×109/L (transfusions are not permitted within 7 days)
d.aspartate aminotransferase (AST) =2.5 x ULN
e.alanine aminotransferase (ALT) =2.5 x ULN
f.total bilirubin =1.5 x ULN, except in subjects with congenital bilirubinemia,such as Gilbert syndrome (direct bilirubin =2.0 x ULN)
g.Estimated creatinine clearance (CrCl) =30 mL/min.Creatinine clearance can be calculated using the Cockcroft-Gault formula (Appendix 8 [Section 10.8]) or eGFR (MDRD; Appendix 9 [Section10.9]), or CKD-epi formula or for subjects
with over- or underweight, CrCl may be measured from a 24-hours urine collection using the formula provided in Appendix 8 [Section 10.8]). If Cockcroft-Gault formula is used and body mass index (BMI) is =30 kg/m2 then adjusted body weight should be used in calculation (Appendix 8 [Section 10.8])
h.corrected serum calcium =13.5 mg/dL (=3.4 mM/L);or free ionized calcium =6.5 mg/dL (=1.6 mM/L)
6.Female subjects of reproductive childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously during the Treatment Period,during any dose interruptions,and for 3months after the last dose of any component of the treatment regimen.Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug.This birth control method must include one highly effective form of
Any potential subject who meets any of the following criteria will be excluded from participating in the study:
1. Frailty index of =2 according to Myeloma Geriatric Assessment score.
2.1 Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg dexamethasone or equivalent).
3. Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other noninvasive lesion that in the opinion of the investigator, with concurrence with the sponsor’s medical monitor, is considered cured with minimal risk of recurrence within 3 years).
4. 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 5.
5.1 Focal radiation therapy within 14 days of randomization with the exception of palliative radiotherapy for symptomatic pain management. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management.
6. Plasmapheresis within 28 days of randomization.
7. Clinical signs of meningeal involvement of multiple myeloma.
8. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted. (FEV1 testing is required for subjects suspected of having COPD).
9. Moderate or severe persistent asthma within the past 2 years, uncontrolled asthma of any classification. (Subjects who have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
10.2 Subject is:
a. Known to be seropositive for human immunodeficiency virus (HIV).
b. 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 total 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 virus (HCV; anti-HCV antibody positive or HCV-RNA quantitation positive), except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy.
11. Concurrent medical or psychiatric condition or disease (such as but not limited to, systemic amyloidosis, POEMS, active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard if enrolled in the study.
12. Has clinically significant cardiac disease, including:
? Myocardial infarction within 6 months before signing the informed consent form (ICF), or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, Ne
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method