A Phase 3 Study Comparing Daratumumab, VELCADE (bortezomib), Lenalidomide, and Dexamethasone (D-VRd) with VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects with Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
- Conditions
- Kahler's diseaseMultiple Myeloma10018865
- Registration Number
- NL-OMON52950
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
Each potential subject must satisfy all of the following criteria to be
enrolled in the study: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 treatment2.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/dL4.Bone lesions:one or more osteolytic lesions on skeletal
radiography,computed tomography (CT),or positron emission tomography
(PET)-CTBiomarkers of Malignancy:a.Clonal bone marrow plasma cell percentage
>=60%b.Involved: uninvolved serum free light chain (FLC)ratio>=100c. >1 focal
lesion on magnetic resonance imaging (MRI) studies3.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 ratio4.Eastern cooperative
oncology group(ECOG) performance status score of 0,1 or25.Clinical laboratory
values meeting the following criteria during the Screening Phase:a.hemoglobin
>=7.5g/dL (>=5 mmol/L) (without prior RBC transfusion within 7days before the
laboratory test;recombinant human erythropoietin use is permitted)b.absolute
neutrophil count (ANC) >= 1.0x10^9/L (granulocyte colony stimulating factor
[G-CSF] use is permitted)c.platelet count >= 70x10^9/L for subjects in whom
<50% of bone marrow nucleated cells are plasma cells;otherwise platelet
count >50×10^9/L (transfusions are not permitted within 7days)d.aspartate
aminotransferase (AST)<=2.5xULNe.alanine aminotransferase (ALT)<=2.5xULNf.total
bilirubin <=1.5xULN,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 (Appendix8),or eGFR (MDRD;Appendix9);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 8h.If Cockcroft-Gault formula
is used and body mass index (BMI) is >or = 30 kg/m² then adjusted body weight
should be used in calculation (Appendix 8 section 10.8)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 in
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. 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. 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 plasmacytima 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. 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of this study is:<br /><br><br /><br>Overall MRD negativity rate, which is defined as the proportion of subjects who<br /><br>have achieved MRD negative status (at 10-5) by bone marrow aspirate after<br /><br>randomization and prior to progressive disease (PD) or subsequent anti-myeloma<br /><br>therapy. Subjects who have<br /><br>achieved MRD negative status on or after PD or after the switch to subsequent<br /><br>anti-myeloma therapy<br /><br>before PD, will not be considered MRD negative in the primary endpoint<br /><br>analysis.</p><br>
- Secondary Outcome Measures
Name Time Method