A phase II study of daratumumab in combination with bortezomib and dexamethasone in patients with multiple myeloma who received 1 prior line of therapy
- Conditions
- Diseases of the blood and blood -forming organs and certain disorders involving the immune mechanism
- Registration Number
- KCT0004352
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 26
1.Subject must be at least 18 years of age.
2.Subject must have documented multiple myeloma as defined by the criteria below:
A.Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy-proven plasmacytoma.
B.Measurable disease as defined by any of the following:
i.Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
ii.IgA multiple myeloma: serum M-protein level =0.5 g/dL or urine M-protein level =200 mg/24 hours; or
iii.Light chain multiple myeloma: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3.Subject must have received 1 prior line of therapy for multiple myeloma, defined as 1 or more cycles of a planned treatment program.
4.Subject must have documented evidence of progressive disease (PD) as defined by the IMWG criteria.
5.Subject must have an ECOG Performance Status score of 0, 1, or 2.
6.For subjects experiencing toxicities resulting from previous therapy (including peripheral neuropathy), the toxicities must be resolved or stabilized to =Grade 1.
7.Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use methods of reliable birth control simultaneously.
8.A woman of childbearing potential must have a negative urine or serum pregnancy test at screening within 10-14 days prior to dosing.
9.Each subject (or their legally acceptable representative) must sign an Informed Consent Form (ICF).
1.Subject has received daratumumab or other anti-CD38 therapies previously.
2.Subject is refractory to bortezomib (ie, subject had progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
3.Subject is intolerant to bortezomib (ie, discontinued due to any adverse event while on bortezomib treatment).
4.Subject has received anti-myeloma treatment within 2 weeks or pharmacokinetic half-lives of the treatment, whichever is longer, before screening.
5.Subjects planning to undergo a stem cell transplant prior to progression of disease on this Study.
6.Subject has a history of malignancy (other than multiple myeloma) within 3 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy 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).
7.Subject has known meningeal involvement of multiple myeloma.
8.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.
9.Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second (FEV1) <60% of predicted normal), asthma, or a history of asthma within the last 2 years. Subjects with known or suspected COPD must have a forced expiratory volume (FEV) test during Screening.
10.Subject is known to be seropositive for human immunodeficiency virus (HIV) or has active hepatitis B or hepatitis C.
11.Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results.
12.Subject has clinically significant cardiac disease, including:
A.Myocardial infarction within 6 months before screening, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV)
B.Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Version 4 Grade 2 or higher) or clinically significant ECG abnormalities.
C.Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >470 msec.
13.Subject has any of the following laboratory test results during the Screening Phase:
A.Absolute neutrophil count =1.0 × 109/L;
B.Hemoglobin level =7.5 g/dL (=5 mmol/L) (it is not permissible to transfuse a subject to reach this level within 2 weeks);
C.Platelet count <75 × 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count <50 × 109/L (it is not permissible to transfuse a subject to reach this level within 1 week);
D.Alanine aminotransferase level =2.5 times the upper limit of normal (ULN);
E.Total bilirubin level =2 × ULN, (except for Gilbert Syndrome: direct bilirubin 2 × ULN);
F.Measured creatinine clearance =15 mL/min/1.73 m2;
14.Subject has known allergies, hypersensitivity, or intolerance to bortezomib, monoclonal antibodies or human proteins, or their excipients or known sensitivity to mammalian-derived products.
15.Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy,
organomegal
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) , Time to progression (TTP) ,Overall response rate (ORR), Overall survival (OS),Time to response (TTR), duration of response (DOR)