A clinical study to compare the safety, effectiveness and pharmacokinetics (the way the body absorbs, distributes, and gets rid of a drug) of Daratumumab given through the subcutaneous route versus the active monitoring in patients with high risk smoldering multiple myeloma (precancerous form of blood cancer in the bone marrow)
- Conditions
- Smoldering multiple myelomaMedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001205-16-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
- Not specified
- Target Recruitment
- 360
Refer to protocol
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. At least 18 years of age or at least the legal age of consent in the jurisdiction in which the study is taking place, whichever is the older age.
2. Diagnosis of SMM for =5 years with measurable disease, defined as serum M protein =10 grams per litre (g/L) or urine M protein =200 milligrams (mg)/24 hours or involved serum free light chain (FLC) =100 milligrams per litre (mg/L) and abnormal serum FLC ratio.
3. Bone marrow plasma cells (BMPCs) =10%; and
At least 1 of the following;
a. Serum M protein =30 g/L,
b. Immunoglobulin A (IgA) SMM,
c. Immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes,
d. Serum involved: uninvolved FLC ratio =8 and < 100, or
e. Clonal BMPCs >50% to <60% with measurable disease.
4. Eastern cooperative oncology group (ECOG) performance status score of 0 or 1.
5. Pretreatment clinical laboratory values: refer to protocol
6. Must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
7. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 1 method highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants], or partner's vasectomy). Contraception must begin 4 weeks prior to dosing. Highly effective contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
8. A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization.
9. During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction.
10. Willing and able to adhere to the prohibitions and restrictions specified in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 216
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144
Refer to protocol
Any potential subject who meets any of the following criteria will be excluded from participating in the study:
1. Multiple myeloma, requiring treatment, defined by any of the following:
a. Bone lesions (one or more osteolytic lesions on low-dose whole body computed tomography [LDCT], positron-emission tomography with computed tomography [PET-CT] or computed tomography [CT])
b. Hypercalcemia (serum calcium >0.25 mmol/L [>1 mg/dL] higher than ULN or >2.75 mmol/L [>11 mg/dL])
c. Renal insufficiency, preferably determined by creatinine clearance <40 mL/min measured or estimated using the modification of diet in renal disease (MDRD), or serum creatinine >177 micro mole per litre (µmol/L)
d. Anemia, defined as hemoglobin <10 gram per deci litre (g/dL) or >2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
e. Clonal BMPC percentage =60%
f. Serum FLC ratio (involved:uninvolved) =100 (The involved FLC must be =100 mg/L)
g. More than 1 focal lesion =5 mm in diameter by magnetic resonance imaging (MRI)
2. Primary systemic (immunoglobulin light chain) amyloidosis (AL)
3. Exposure to any of the following
a. Prior exposure to daratumumab or prior exposure to other anti-CD38 therapies
b. Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate as indicated for osteoporosis is acceptable.
c. Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1
d. Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization; or >280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization
4. Received treatment for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion, which is considered cured with minimal risk of recurrence within 3 years.
5. Either of the following:
a. Known or suspected chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
b. 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)
6. Any of the following:
a. Known to be seropositive for human immunodeficiency virus (HIV)
b. Known to be seropositive for hepatitis B (defined by a positive test for hepatitis B surface and antigen [HBsAg]) or with known prior hepatitis B infection without evidence of immunity (ie, subjects who are positive for antibodies to hepatitis B
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