A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants with Smoldering Multiple Myeloma

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 62

Inclusion Criteria

- diagnosis of smoldering multiple myeloma (SMM) for less than 5 years
- have a confirmed diagnosis of intermediate or high-risk SMM, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

1. Active MM, requiring treatment, defined by any of the following:
a. Bone lesions (one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron-emission tomography [PET]-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 (see Section 9.2.1.4; preferably determined by creatinine clearance <40 mL/min measured or estimated using validated equations [MDRD or CKD-EP formulae recommended], or serum creatinine >177 µmol/L [>2 mg/dL])
d. Anemia, defined as hemoglobin <10 g/dL and/or >2 g/dL below LLN in the absence of transfusion support or concurrent treatment with erythropoietin stimulating agents (ESAs)
e. Clonal bone marrow plasma cell percentage =60%
f. Serum free light chain involved:uninvolved ratio =100
g. More than 1 focal lesion by magnetic resonance imaging (MRI)
2. Primary systemic AL (immunoglobulin light chain) amyloidosis
3. Prior or concurrent exposure to any of the following:
- To approved or investigational treatments for SMM or/and MM (including but not limited to conventional chemotherapies, immunomodulatory drugs (IMiDs), or proteasome inhibitors).
- To daratumumab or other anti CD-38 therapies
- To concurrent treatment with corticosteroids with a dose >10 mg prednisone per day or equivalent.
- To concurrent treatment with bone-protecting agents (eg, bisphosphonates, denosumab) for treatment of SMM or MM. The subjects who are on a stable dose of these medications for a nonmalignant condition are allowed in the study.
- Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1
4. Subject has a history of malignancy (other than SMM) within 3 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix.
a) Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
b) Subject has known moderate or severe persistent asthma within the past 2 years (see Attachment 2), 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. Subject is:
- known to be seropositive for human immunodeficiency virus (HIV).
- known to have a history of hepatitis C.
- 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 hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be tested 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 (antiHBs 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.
For subjects who e

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate if daratumumab can effectively decrease M protein in subjects with intermediate or high-risk SMM as assessed by CR rate<br>- To determine if daratumumab reduces the progression/death rate in subjects with intermediate or high-risk SMM;Secondary Objective: - To evaluate preliminary efficacy, including Overall Response Rate (ORR) and progressionfree survival (PFS)<br>- To evaluate the minimal residual disease (MRD) negative rate<br>- To evaluate the pharmacokinetics and immunogenicity of daratumumab<br>- To assess the safety profile of daratumumab given in 3 different dosing schedules<br>- To determine if daratumumab has an effect on QT interval;Primary end point(s): 1. The percentage of participants who achieve a complete response (CR)<br>2. The percentage of participants that have an event (disease progression or death) per patient-year;Timepoint(s) of evaluation of this end point: Up to approximately 24 months for point 1.<br>Up to approximately 30 months for point 2.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. The percentage of participants who are minimal residual disease (MRD) negative.<br>2. Time to next treatment (TNT).<br>3. The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR)<br>4. The median time of progression free survival (PFS)<br>5. The percentage of participants with symptomatic multiple myeloma<br>6. Response to first subsequent multiple myeloma treatment<br>7. Overall survival rate;Timepoint(s) of evaluation of this end point: Up to 5.5 years

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