A clinical study to compare the effectiveness and pharmacokinetics (the way the body absorbs, distributes, and gets rid of a drug) of Daratumumab given through the subcutaneous route versus the intravenous route in patients with relapsed or refractory multiple myeloma (blood cancer in the bone marrow)
- Conditions
- Multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000206-38-GB
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 480
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1.At least 18 years of age
2.documented with multiple myeloma as defined by the criteria below:
a)Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b)Measurable disease at Screening as defined by any of the following:
i) Serum M-protein level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
ii) Light chain multiple myeloma without measurable disease in the serum or the urine:
Serum immunoglobulin FLC =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
3. Evidence of a response (partial response [PR] or better based on investigator's determination of response by IMWG criteria) to at least 1 prior treatment regimen.
4. Relapsed or refractory disease as defined below:
a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed PD by IMWG criteria greater than (>) 60 days after cessation of treatment.
b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or > 60 days after cessation of treatment.
5. Received at least 3 prior lines of therapy including a PI (=2 cycles or 2 months of treatment) and an IMiD (= 2 cycles or 2 months of treatment) in any order during the course of treatment (except for subjects who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy
OR
Refractory to both a PI and an IMiD. For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMiD, their disease must be refractory to the most recent one.
6. Eastern cooperative oncology group (ECOG) performance Status score of 0, 1, or 2
7. Subjects who has pretreatment clinical laboratory values meeting the following criteria during the screening phase:
a) Hemoglobin =7.5 gram per decilitre (g/dL) (= 5 millimoles per litre [mmol/L])(without prior red blood cells [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)
b) Absolute neutrophil count >= 1.0 × 10^9/Litre (L)
c) Platelet count >= 50 × 10^9/L (transfusions are not permitted within 7 days of testing to achieve this minimum platelet count)
d) Aspartate aminotransferase (AST) <= 2.5 × upper limit of normal (ULN)
e) Alanine aminotransferase (ALT) <= 2.5 × ULN
f) Total bilirubin <= 2.0 × ULN; except in subjects with congenital bilirubinemia, such as Gilbert syndrome
g) Estimated creatinine clearance > 20 milliletre per minute (mL/min) per 1.73m^2
h) Albumin-corrected serum calcium <=14 mg/dL (<= 3.5 mmol/L) or free ionized calcium <= 6.5 mg/dL (<=1.6 mmol/L).
8. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or i
1.Subjects who received daratumumab or other anti-CD38 therapies previously
2.Subjects who received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer,before the date of randomization.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
3.Subjects who received autologous stem cell transplant within 12weeks before the date of randomization,or the subject has previously received allogeneic stem cell transplant (regardless of timing)
4.Subjects who has plans to undergo a stem cell transplant prior to progression of disease on this study
5.History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive 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.
6.Subjects with clinical signs of meningeal involvement of multiple myeloma
7.Subjects with either of the following:
a)Known chronic obstructive pulmonary disease(COPD)with a forced expiratory volume in 1 second (FEV1) is <50% of predicted normal
b)Known moderate or severe persistent asthma,or a history of asthma within the last 2 years,or currently has uncontrolled asthma of any classification (Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study)
8.Subjects with any of the following:
a)Known to be seropositive for human immunodeficiency virus(HIV)
b)Known to be hepatitis B (hepatitis B surface antigen [HBsAg]positive,or antibodies to hepatitis B surface or core antigens [antiHBs or antiHBc]with hepatitis B virus [HBV]-DNA quantitation positive).Subjects who are positive for antiHBs or antiHBc must have a negative polymerase chain reaction (PCR) for HBV-DNA quantitation result at screening. Those who are PCR positive will be excluded
c)Known to be seropositive for hepatitisC
9.Subjects with concurrent medical or psychiatric condition or disease (example,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 for participating in this study
10.Subjects with clinically significant cardiac disease,including:
a)Myocardial infarction within 6 months before date of randomization,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)Uncontrolled cardiac arrhythmia (Grade 2 or higher)or clinically significant electrocardiogram (ECG) abnormalities.
c)Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula >470 msec.
11.Subjects with known allergies,hypersensitivity,or intolerance to any of the study drugs,hyaluronidase,mAbs,human proteins, or their excipients, or known sensitivity to mammalian-derived products.
12.Subjects with plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome or amyloido
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