TriangleNCT03301220 · CITED IN SOURCE DOCUMENTS
A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2026-06-08
The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
Time to Biochemical or Diagnostic (SLiM-CRAB) Progression Per Computerized Algorithm Analyses
Overall Response Rate (ORR)
Complete Response (CR) Rate
Time to First-Line Treatment for Multiple Myeloma
Progression-Free Survival on First-Line Treatment for Multiple Myeloma (PFS2)
Best Response on First-line Therapy for Multiple Myeloma
Overall Survival (OS)
Percentage of Participants Who Progressed to Multiple Myeloma With Adverse Prognostic Features
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Minimum Observed Serum Concentration (Cmin) of Daratumumab
Number of Participants With Anti-daratumumab Antibodies
Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire Score
Duration of Response
Time to Response
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group \[IMWG\] criteria) for less than or equal to (\<=) 5 years with measurable disease at the time of randomization, defined as serum M protein greater than or equal to (\>=) 10 gram per liter (g/L) or urine M protein \>= 200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) \>=100 milligram per liter (mg/L) and abnormal serum FLC ratio * Clonal bone marrow plasma cells (BMPCs) \>= 10 percentage (%); and at least 1 of the following risk factors; Serum M protein \>= 30 g/L, immunoglobulin (Ig)A SMM, immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM, and IgG should be considered in determination for immunoparesis; IgD and IgE are not considered in this assessment), serum involved: uninvolved FLC ratio \>= 8 and less than (\<) 100, or clonal BMPCs greater than (\>) 50% to \<60% with measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 * Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective method of contraception * A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization * 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 Exclusion Criteria: * Multiple myeloma (MM), requiring treatment, defined by any of the following: 1. Bone lesions (1 or more osteolytic lesions on low-dose whole body computed tomography \[LDCT\], positron-emission tomography with computed tomography \[PET-CT\] or CT). Participants who have benign/post-traumatic bone lesions visible on screening images as well as previous imaging, may be considered for inclusion. Details (diagnosis, location, duration) on benign/post-traumatic pre-existing bone lesions that can be seen on the screening images (example \[eg.\], old fractures) and were also present on previous imaging are to be reported in the case report form (CRF) 2. Hypercalcemia (serum calcium greater than \[\>\]0.25 millimoles per liter \[mmol/L\] \[\>1 milligram per deciliter {mg/dL}\] higher than upper limit of normal \[ULN\] or \>2.75 mmol/L \[\>11 mg/dL\]). Participants who have clinically stable hypercalcemia attributable to a disease other than multiple myeloma (eg, hyperparathyroidism) may be considered for inclusion after a case by case review by the medical monitor 3. Renal insufficiency, preferably determined by creatinine clearance less than (\<)40 milliliter per minute (mL/min) measured or estimated using the Modification of Diet in Renal Disease (MDRD), or serum creatinine \>177 micromole per liter (μmol/L). Participants who have clinically stable renal insufficiency attributable to a disease other than multiple myeloma (eg, glomerulonephritis) may be considered for inclusion after a case by case review by the medical monitor 4. Anemia, defined as hemoglobin \<10 gram per deciliter (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. Participants who have clinically stable anemia attributable to a disease other than multiple myeloma (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for inclusion after a case by case review by the medical monitor 5. Clonal BMPC percentage \>=60% 6. Serum FLC ratio (involved:uninvolved) \>=100 (the involved FLC must be \>=100 mg/L) 7. More than 1 focal lesion \>=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI) * Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis * Exposure to any of the following: 1. Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies 2. 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 and denosumab as indicated for osteoporosis is acceptable 3. 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 4. Ongoing treatment with corticosteroids with a dose \>10 milligram (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 5. Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab), immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or other treatments that are likely to interfere with the study procedures or results * Received treatment (chemotherapy, surgery, et cetera \[etc\]) 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 * Medical or psychiatric condition or disease (for example, active systemic disease \[including presence of auto-antibodies\], uncontrolled diabetes) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study * Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, hyaluronidase, or other human proteins, or their excipients, or known sensitivity to mammalian-derived products (including dairy allergy)
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants randomized to active monitoring will receive no study medication, but will undergo the same disease evaluations at the same frequency as participants randomized to daratumumab.
- label
- Arm A: Active Monitoring
- type
- NO_INTERVENTION
- description
- Participants will receive 1800 milligram (mg) of daratumumab co-formulated with 2000 units per milliliter (U/mL) of recombinant human hyaluronidase (rHuPH20) by subcutaneous (SC) injection until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion.
- intervention Names
- Drug: Daratumumab SC: daratumumab + rHuPH20
- label
- Arm B: Daratumumab SC
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm B: Daratumumab SC
- description
- Participants will receive daratumumab SC injection (daratumumab 1800 mg + rHuPH20 \[2000 U/mL\]) once weekly for Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks for Cycle 3 to Cycle 6 (Days 1 and 15), and thereafter every 4 weeks (Day 1) until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion. Each cycle is 28 days in duration.
- name
- Daratumumab SC: daratumumab + rHuPH20
- other Names
- JNJ-54767414
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 390
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS was defined as the duration from the date of randomization to either progressive to multiple myeloma (MM), according to the International Myeloma Working Group (IMWG) diagnostic criteria for MM, or death due to any cause, whichever occurred first. Per IMWG criteria, active MM by SLiM-CRAB defined as: greater than or equal to (\>=) 60 percent (%) bone marrow plasma cells (BMPCs), free light chain (FLC) involved/uninvolved ratio \>=100, greater than (\>)1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions. Kaplan-Meier estimate was used.
- measure
- Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)
- time Frame
- From randomization (Day -5) up to 77 months
- secondary Outcomes
- measure
- Time to Biochemical or Diagnostic (SLiM-CRAB) Progression Per Computerized Algorithm Analyses
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Overall Response Rate (ORR)
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Complete Response (CR) Rate
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Time to First-Line Treatment for Multiple Myeloma
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Progression-Free Survival on First-Line Treatment for Multiple Myeloma (PFS2)
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Best Response on First-line Therapy for Multiple Myeloma
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Overall Survival (OS)
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Percentage of Participants Who Progressed to Multiple Myeloma With Adverse Prognostic Features
- time Frame
- From randomization (Day -5) up to 8 years
- measure
- Maximum Observed Serum Concentration (Cmax) of Daratumumab
- time Frame
- Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT, 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
- measure
- Minimum Observed Serum Concentration (Cmin) of Daratumumab
- time Frame
- Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT( 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
- measure
- Number of Participants With Anti-daratumumab Antibodies
- time Frame
- Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
- measure
- Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies
- time Frame
- Cycles 1, 3, 5, 7, 12, and 24 : Predose on Day 1; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Full study description
- brief Summary
- The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).
Source references
- references
- citation
- Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, Lindsay J, Baker RI, Suzuki K, Kosugi H, Levin MD, Beksac M, Stockerl-Goldstein K, Oriol A, Mikala G, Garate G, Theunissen K, Spicka I, Mylin AK, Bringhen S, Uttervall K, Pula B, Medvedova E, Cowan AJ, Moreau P, Mateos MV, Goldschmidt H, Ahmadi T, Sha L, Cortoos A, Katz EG, Rousseau E, Li L, Dennis RM, Carson R, Rajkumar SV; AQUILA Investigators. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. N Engl J Med. 2025 May 8;392(18):1777-1788. doi: 10.1056/NEJMoa2409029. Epub 2024 Dec 9.
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Preserved source evidence · Not medical advice