A Phase 2 interventional study of daratumumab and daratumumab in Multiple Myeloma, sponsored by Janssen Research & Development, LLC. Completed at 57 sites in 11 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-23.
Sponsored by Janssen Research & Development, LLC · Phase 2, Interventional, and Treatment
The purpose of this study is to evaluate three daratumumab dose schedules in participants with Smoldering Multiple Myeloma.
This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab in participants diagnosed with intermediate or high-risk Smoldering Multiple Myeloma (SMM [ie, early disease without any symptoms]). Participants will be randomized (assigned by chance) to one of 3 treatment groups (arm A [long intense], arm B [intermediate] and arm C [short intense]) to receive daratumumab. Each treatment group will investigate 1 of 3 dosing schedules of daratumumab. The study will include a 28-Day Screening Phase, a Treatment Phase of 1 to 20 treatment cycles (each cycle is 8 weeks in duration for total period of 8 to 160 weeks), and a Follow up Phase of 4-weeks from the last dose of study drug. For participants in Arm A (long intense) and Arm B (intermediate), there is a possibility to extend treatment with IV daratumumab (Q8W) after the end of Cycle 20 if, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade >=3 treatment related toxicity, and at least stable disease has been achieved. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w). The Follow-up Phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. The end of the study will occur approximately 7 years after the last participant enrolled receives a first dose of study drug. 'Disease assessment will be performed locally per Standard of Care.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 123 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
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Exclusion Criteria:
Drug: daratumumab
Drug: daratumumab
Drug: daratumumab
16 mg/kg administered by intravenous (IV) infusion once every week in Cycle 1, every other week in Cycle 2 and Cycle 3, every 4 weeks in Cycle 4 to Cycle 7, and from Cycle 8 to Cycle 20 on Day 1 of each cycle. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (\>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w).
16 mg/kg administered by IV infusion once every week in Cycle 1, and then on Day 1 of each cycle from Cycle 2 to Cycle 20, and every 8 weeks after Cycle 20. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (\>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w).
16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.
Percentage of Participants Who Achieved a Complete Response (CR) by International Myeloma Working Group (IMWG) Criteria
Percentage of participants who achieved a CR by IMWG Criteria were reported. CR was defined as CR plus stringent complete Response (sCR) by IMWG criteria. Per IMWG criteria, CR response was defined as a negative immunofixation on the serum and urine, and less than (\<) 5 percentage (%) plasma cells in bone marrow; sCR was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
Time frame: From Cycle 1 Day 1 up to 1.58 years
Progressive Disease or Death Rate
Progressive disease (PD) or death rate were reported. PD or death rate per patient-year was defined as number of events (PD or death) divided by total progression-free survival (PFS) for all participants.
Time frame: From Cycle 1 Day 1 up to 2.07 years
Minimal Residual Disease (MRD) Negative Rate
MRD negative rate were reported. The MRD negativity rate was defined as the percentage of participants with a CR or better response who had negative MRD (10\^-4 and 10\^-5) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates at any time after the randomization and prior to progressive disease, subsequent therapy.
Time frame: From Cycle 1 Day 1 up to 91.6 months
Time to Next Treatment (TNT) for Active Myeloma
Time to next treatment (TNT) for active myeloma were reported. Time to next treatment was defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment. Kaplan-Meier estimate was used.
Time frame: From randomization (Day -5) up to the date of first subsequent antimyeloma treatment (up to 7.89 years)
Percentage of Participants Who Achieved Partial Response or Better Response (Stringent Complete Response [sCR] Plus Complete Response [CR] Plus Very Good Partial Response [VGPR] or a Partial Response [PR])
Per IMWG criteria, CR: was defined as a negative immunofixation on serum and urine, and \<5% plasma cells in bone marrow; sCR: CR plus normal FLC ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hours; PR: \>=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% in difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein were not measurable and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required in place of M-protein, provided baseline bone marrow plasma cells percentage was \>=30%.
Time frame: From start of the treatment (Cycle 1 Day 1) until confirmed PD, death, start of new anticancer therapy, withdrawal of consent, lost to follow-up, or end of the study, whichever occurred first (up to 7.89 years)
Progression Free Survival (PFS)
PFS: time from dates of randomization to initial documented PD per Sixty percent, bone marrow plasma cells (BMPC), Light chains, focal lesions per MRI, elevated Calcium, Renal failure, Anemia, Bone lesions (SLiM-CRAB) criteria, or date of death, whichever was first. SLiM-CRAB criteria: clonal BM PCs percentage (%): \>=60%, Involved: uninvolved serum free LC ratio \>=100, \>1 focal lesion on MRI studies, calcium:\>0.25 millimole/liter (mmol/L)(\>1 mg/dL) higher than upper limit of normal or \>2.75 mmol/L (\>11 mg/dL); creatinine clearance \<40 mL/min or serum creatinine \>177 micromole/liter (\>2 mg/dL); hemoglobin \<10 g/dL(\<6.5 mmol/L) or \>2 g/dL(\>1.25 mmol/L) lower than lower limit of normal;\>1 osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT). Kaplan-Meier estimate was used.
Time frame: From randomization (Day -5) until disease progression or death whichever occurred first (up to 7.89 years)
Percentage of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features
Percentage of participants with symptomatic multiple myeloma with adverse prognostic features were reported. The International Staging System (ISS) for multiple myeloma (MM) was based on serum beta-2 microglobulin (S beta-2M) and serum albumin; that is, participants progressed to symptomatic multiple myeloma (SymT MM) with stage III (S beta2M\>= 5.5 mg/L) of ISS, Participants progressed to SymT MM with adverse cytogenetic characteristics (ACC), participants progressed to SymT MM with stage III of ISS or adverse cytogenetic characteristics. Adverse cytogenetic characteristics included Fluorescence in situ hybridization (FISH) findings of del(17p13), t(14;16), t(4;14), amp(1q21) or karyotype findings of t(4;14), del(17p) or a combination of these.
Time frame: From start of treatment (Cycle 1 Day 1) until PD or prior to any subsequent anti-Multiple myeloma therapy (up to 7.89 years)
Number of Participants With Response to First Subsequent Multiple Myeloma Treatment
Response (IMWG Criteria) to first subsequent MM treatment: sCR: CR + normal FLC ratio and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: a negative immunofixation on serum and urine, and \<5% plasma cells in BM; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein \<100mg/24 hours; PR:\>=50% reduction of serum M-protein and \>=90% reduction in urine M-protein in 24 hour or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required instead of M-protein, provided bone marrow plasma cells percentage was \>=30%.
Time frame: From Cycle 1 Day 1 up to 7.89 years
Overall Survival
Overall Survival (OS) was defined as the time from the date of randomization to the date of death. Median OS was estimated by using the Kaplan-Meier method.
Time frame: From randomization (Day -5) till death (up to 7.89 years)
| Milestone | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Started | 41 | 41 | 41 |
| Participants who entered extension phase | 21 | 15 | 0 |
| Participants switched: daratumumab iv to sc | 16 | 10 | 0 |
| Treated | 41 | 41 | 40 |
| Completed | 1 | 0 | 0 |
| Not completed | 40 | 41 | 41 |
| Withdrew: Withdrawal by subject | 3 | 4 | 9 |
| Withdrew: Other | 1 | 1 | 1 |
| Withdrew: Death | 7 | 5 | 4 |
| Withdrew: End of data collection | 29 | 31 | 27 |
Percentage of participants who achieved a CR by IMWG Criteria were reported. CR was defined as CR plus stringent complete Response (sCR) by IMWG criteria. Per IMWG criteria, CR response was defined as a negative immunofixation on the serum and urine, and less than (\<) 5 percentage (%) plasma cells in bone marrow; sCR was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
| percentage of participants | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Percentage of Participants Who Achieved a Complete Response (CR) by International Myeloma Working Group (IMWG) Criteria | 4.9 | 12.2 | 0 |
Progressive disease (PD) or death rate were reported. PD or death rate per patient-year was defined as number of events (PD or death) divided by total progression-free survival (PFS) for all participants.
| events per patient-year | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Progressive Disease or Death Rate | 0.096 | 0.102 | 0.109 |
MRD negative rate were reported. The MRD negativity rate was defined as the percentage of participants with a CR or better response who had negative MRD (10\^-4 and 10\^-5) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates at any time after the randomization and prior to progressive disease, subsequent therapy.
| percentage of participants | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| MRD (10^-4) | 2.4 | 7.3 | 0 |
| MRD (10^-5) | 0 | 0 | 0 |
Time to next treatment (TNT) for active myeloma were reported. Time to next treatment was defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment. Kaplan-Meier estimate was used.
| months | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Time to Next Treatment (TNT) for Active Myeloma | NA (NA to NA) | NA (59.9 to NA) | 76.3 (40.4 to 80.3) |
Per IMWG criteria, CR: was defined as a negative immunofixation on serum and urine, and \<5% plasma cells in bone marrow; sCR: CR plus normal FLC ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hours; PR: \>=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% in difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein were not measurable and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required in place of M-protein, provided baseline bone marrow plasma cells percentage was \>=30%.
| percentage of participants | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Percentage of Participants Who Achieved Partial Response or Better Response (Stringent Complete Response [sCR] Plus Complete Response [CR] Plus Very Good Partial Response [VGPR] or a Partial Response [PR]) | 56.1 (42.1 to 69.4) | 56.1 (42.1 to 69.4) | 37.5 (24.7 to 51.7) |
PFS: time from dates of randomization to initial documented PD per Sixty percent, bone marrow plasma cells (BMPC), Light chains, focal lesions per MRI, elevated Calcium, Renal failure, Anemia, Bone lesions (SLiM-CRAB) criteria, or date of death, whichever was first. SLiM-CRAB criteria: clonal BM PCs percentage (%): \>=60%, Involved: uninvolved serum free LC ratio \>=100, \>1 focal lesion on MRI studies, calcium:\>0.25 millimole/liter (mmol/L)(\>1 mg/dL) higher than upper limit of normal or \>2.75 mmol/L (\>11 mg/dL); creatinine clearance \<40 mL/min or serum creatinine \>177 micromole/liter (\>2 mg/dL); hemoglobin \<10 g/dL(\<6.5 mmol/L) or \>2 g/dL(\>1.25 mmol/L) lower than lower limit of normal;\>1 osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT). Kaplan-Meier estimate was used.
| months | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Progression Free Survival (PFS) | 81.12 (58.02 to NA) | 84.44 (44.02 to NA) | 81.35 (51.45 to NA) |
Percentage of participants with symptomatic multiple myeloma with adverse prognostic features were reported. The International Staging System (ISS) for multiple myeloma (MM) was based on serum beta-2 microglobulin (S beta-2M) and serum albumin; that is, participants progressed to symptomatic multiple myeloma (SymT MM) with stage III (S beta2M\>= 5.5 mg/L) of ISS, Participants progressed to SymT MM with adverse cytogenetic characteristics (ACC), participants progressed to SymT MM with stage III of ISS or adverse cytogenetic characteristics. Adverse cytogenetic characteristics included Fluorescence in situ hybridization (FISH) findings of del(17p13), t(14;16), t(4;14), amp(1q21) or karyotype findings of t(4;14), del(17p) or a combination of these.
| percentage of participants | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Participants with stage III of ISS | 2.4 | 0 | 0 |
| Participants with ACC | 19.5 | 12.2 | 9.8 |
| Participants with stage III of ISS staging or ACC | 22.0 | 12.2 | 9.8 |
Response (IMWG Criteria) to first subsequent MM treatment: sCR: CR + normal FLC ratio and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: a negative immunofixation on serum and urine, and \<5% plasma cells in BM; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>=90% reduction in serum M-protein plus urine M-protein \<100mg/24 hours; PR:\>=50% reduction of serum M-protein and \>=90% reduction in urine M-protein in 24 hour or to \<200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of \>=50% difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells was required instead of M-protein, provided bone marrow plasma cells percentage was \>=30%.
| Participants | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Number of Participants With Response to First Subsequent Multiple Myeloma Treatment | 6 | 12 | 15 |
Overall Survival (OS) was defined as the time from the date of randomization to the date of death. Median OS was estimated by using the Kaplan-Meier method.
| months | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| Overall Survival | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
Collected over All-Cause Mortality: From randomization (Day -5) up to 7.89 years; Serious Adverse Events and Other Adverse Events: From Cycle 1 Day 1 up to 7.89 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (Long Intense) | 7/41 (17.1%) | 20/41 (48.8%) | 38/41 (92.7%) |
| Arm B (Intermediate) | 5/41 (12.2%) | 14/41 (34.1%) | 41/41 (100%) |
| Arm C (Short Intense) | 4/41 (9.8%) | 4/40 (10%) | 32/40 (80%) |
| Event | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| PneumoniaInfections and infestations | 4/41 | 1/41 | 1/40 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/41 | 2/41 | 0/40 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 0/41 | 2/41 | 0/40 |
| Angina PectorisCardiac disorders | 0/41 | 0/41 | 1/40 |
| Angina UnstableCardiac disorders | 0/41 | 0/41 | 1/40 |
| SepsisInfections and infestations | 1/41 | 0/41 | 1/40 |
| LeukocytosisBlood and lymphatic system disorders | 1/41 | 0/41 | 0/40 |
| Acute Coronary SyndromeCardiac disorders | 0/41 | 1/41 | 0/40 |
| Atrial FibrillationCardiac disorders | 1/41 | 0/41 | 0/40 |
| Atrioventricular BlockCardiac disorders | 0/41 | 1/41 | 0/40 |
| Event | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) |
|---|---|---|---|
| FatigueGeneral disorders | 19/41 | 25/41 | 9/40 |
| Upper Respiratory Tract InfectionInfections and infestations | 20/41 | 15/41 | 4/40 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 14/41 | 19/41 | 1/40 |
| CoughRespiratory, thoracic and mediastinal disorders | 18/41 | 15/41 | 11/40 |
| DiarrhoeaGastrointestinal disorders | 14/41 | 13/41 | 4/40 |
| InsomniaPsychiatric disorders | 13/41 | 14/41 | 5/40 |
| HeadacheNervous system disorders | 13/41 | 10/41 | 13/40 |
| Back PainMusculoskeletal and connective tissue disorders | 10/41 | 12/41 | 4/40 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 12/41 | 8/41 | 3/40 |
| NauseaGastrointestinal disorders | 10/41 | 11/41 | 3/40 |
| Age, Continuous(years) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Mean | 62.4 ± 9.86 | 61.5 ± 8.76 | 59.0 ± 10.55 | 61 ± 9.78 |
| Sex: Female, Male(Participants) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Female | 24 | 24 | 20 | 68 |
| Male | 17 | 17 | 21 | 55 |
| Ethnicity (NIH/OMB)(Participants) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 2 | 0 | 2 |
| Not Hispanic or Latino | 40 | 38 | 39 | 117 |
| Unknown or Not Reported | 1 | 1 | 2 | 4 |
| Race (NIH/OMB)(Participants) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 0 | 1 |
| Asian | 2 | 1 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 2 | 1 | 2 | 5 |
| White | 35 | 37 | 35 | 107 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 2 | 3 | 6 |
| Region of Enrollment(Participants) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Australia | 2 | 3 | 5 | 10 |
| Canada | 2 | 6 | 1 | 9 |
| France | 1 | 1 | 4 | 6 |
| Germany | 0 | 1 | 5 | 6 |
| Israel | 6 | 6 | 1 | 13 |
| Italy | 3 | 2 | 4 | 9 |
| Netherlands | 2 | 1 | 3 | 6 |
| Russian Federation | 2 | 2 | 3 | 7 |
| Turkey | 5 | 1 | 3 | 9 |
| United Kingdom | 2 | 7 | 1 | 10 |
| United States | 16 | 11 | 11 | 38 |
| Stage of Disease (ISS)(Participants) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Stage I | 30 | 34 | 34 | 98 |
| Stage II | 8 | 7 | 7 | 22 |
| Stage III | 3 | 0 | 0 | 3 |
| Weight(Kilograms (Kg)) | Arm A (Long Intense) | Arm B (Intermediate) | Arm C (Short Intense) | Total |
|---|---|---|---|---|
| Mean | 81.11 ± 17.434 | 78.87 ± 18.471 | 80.04 ± 13.481 | 80.01 ± 16.491 |
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Janssen Research & Development, LLC