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)

A Phase 3 Randomized, Multicenter Study of Subcutaneous Daratumumab Versus Active Monitoring in Subjects with High-risk Smoldering Multiple Myeloma

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-001205-16-BE

Enrollment

360

Registered

2017-09-01

Start date

2017-10-18

Completion date

Unknown

Last updated

2024-02-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Smoldering multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Interventions

Trade Name: Darzalex Product Name: Daratumumab co-formulated with recombinant human hyaluronidase (rHuPH20) Product Code: JnJ 54767414 Pharmaceutical Form: Injection INN or Proposed INN: DARATUMUMAB C

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 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 50% to =65 years) yes F.1.3.1 Number of subjects for this age range 144

Exclusion criteria

Exclusion criteria: 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 177 micro mole per litre (µmol/L) d. Anemia, defined as hemoglobin 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. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Local testing and results of hepatitis B serology (Includes HBsAg, anti-HBs, and anti-HBc) is required for all patients prior to randomization when this amendment 3 is implemented. 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 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) A

Design outcomes

Primary

Measure	Time frame
Main Objective: The main objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in subjects with high-risk smoldering multiple myeloma (SMM).;Secondary Objective: -To demonstrate additional clinical benefit (ORR, duration of response, OS, etc) for subjects with high-risk SMM treated with daratumumab compared with active monitoring - To assess the safety profile of daratumumab in subjects with high-risk SMM - To assess the clinical characteristics of symptomatic MM following progression of disease after therapy with daratumumab - To evaluate the PK and immunogenicity of daratumumab administered SC in subjects with high-risk SMM - To evaluate the immunogenicity of rHuPH20 when administered in combination with daratumumab SC in subjects with high-risk SMM - To evaluate the effect of treatment with daratumumab on health-related quality of life (HRQoL);Primary end point(s): Progression-free survival (PFS), defined as the time from the date of randomization to the date of initial documented progression to MM according to the international myeloma working group (IMWG) diagnostic criteria for MM or the date of death, whichever occurs first;Timepoint(s) of evaluation of this end point: Every 12 weeks until progressive disease	—

Measure

Time frame

Main Objective: The main objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in subjects with high-risk smoldering multiple myeloma (SMM).;Secondary Objective: -To demonstrate additional clinical benefit (ORR, duration of response, OS, etc) for subjects with high-risk SMM treated with daratumumab compared with active monitoring - To assess the safety profile of daratumumab in subjects with high-risk SMM - To assess the clinical characteristics of symptomatic MM following progression of disease after therapy with daratumumab - To evaluate the PK and immunogenicity of daratumumab administered SC in subjects with high-risk SMM - To evaluate the immunogenicity of rHuPH20 when administered in combination with daratumumab SC in subjects with high-risk SMM - To evaluate the effect of treatment with daratumumab on health-related quality of life (HRQoL);Primary end point(s): Progression-free survival (PFS), defined as the time from the date of randomization to the date of initial documented progression to MM according to the international myeloma working group (IMWG) diagnostic criteria for MM or the date of death, whichever occurs first;Timepoint(s) of evaluation of this end point: Every 12 weeks until progressive disease

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Secondary

Measure	Time frame
Secondary end point(s): 1. Time to biochemical or diagnostic (SLiM-CRAB) progression defined as the earlier of time to the earlier of biochemical progression or diagnostic (SLiM-CRAB) progression 2. Overall response rate (ORR), defined as, the proportion of subjects with a PR or better as defined by the IMWG response criteria 3. Complete response (CR) rate, defined as, the proportion of subjects with a CR (or better) as defined by the IMWG response criteria 4. Time to first-line treatment for MM, defined as, the time from the date of randomization to the date of the first-line treatment for MM 5. Progression-free survival on first-line treatment for MM (PFS2), defined as, the time from the date of randomization to the date of documented progressive disease (PD) on the first-line treatment for MM or death, whichever comes first 6. Overall survival (OS), defined as, the time from the date of randomization to the date of death 7. Incidence of MM with adverse prognostic features, which include International Staging System Stage III (based on ß2-microglobulin and albumin) and adverse cytogenetic characteristics 8. Serum daratumumab PK concentrations and parameters including minimum observed concentration (Cmin) and maximum observed concentration (Cmax) 9. Incidence of anti-daratumumab antibodies and anti-rHuPH20 antibodies 10. Change from baseline in global health status and emotional functioning scales of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30, future perspective scale of the EORTC QLQ-MY20, and utility and visual analog scale of the European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) 11. Duration of response, defined as date of onset of first response until date of disease progression or death 12. Time to response, defined as the time from randomization until onset of first response Exploratory end point: 13. Identification of novel biomarkers in relation to PFS/OS ;Timepoint(s) of e	—

Measure

Time frame

Secondary end point(s): 1. Time to biochemical or diagnostic (SLiM-CRAB) progression defined as the earlier of time to the earlier of biochemical progression or diagnostic (SLiM-CRAB) progression 2. Overall response rate (ORR), defined as, the proportion of subjects with a PR or better as defined by the IMWG response criteria 3. Complete response (CR) rate, defined as, the proportion of subjects with a CR (or better) as defined by the IMWG response criteria 4. Time to first-line treatment for MM, defined as, the time from the date of randomization to the date of the first-line treatment for MM 5. Progression-free survival on first-line treatment for MM (PFS2), defined as, the time from the date of randomization to the date of documented progressive disease (PD) on the first-line treatment for MM or death, whichever comes first 6. Overall survival (OS), defined as, the time from the date of randomization to the date of death 7. Incidence of MM with adverse prognostic features, which include International Staging System Stage III (based on ß2-microglobulin and albumin) and adverse cytogenetic characteristics 8. Serum daratumumab PK concentrations and parameters including minimum observed concentration (Cmin) and maximum observed concentration (Cmax) 9. Incidence of anti-daratumumab antibodies and anti-rHuPH20 antibodies 10. Change from baseline in global health status and emotional functioning scales of the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30, future perspective scale of the EORTC QLQ-MY20, and utility and visual analog scale of the European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) 11. Duration of response, defined as date of onset of first response until date of disease progression or death 12. Time to response, defined as the time from randomization until onset of first response Exploratory end point: 13. Identification of novel biomarkers in relation to PFS/OS ;Timepoint(s) of e

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Countries

Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

Public ContactClinical Registry group

Janssen-Cilag International N.V.

ClinicalTrialsEU@its.jnj.com+31715242166

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026