54767414SMM2001

Janssen-Cilag International NV

Turnhoutseweg 30, Beerse, Belgium, B-2340

Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com

Clinical Registry Group, Janssen-Cilag International NV, ClinicalTrialsEU@its.jnj.com

No

No

No

Final

02 Jun 2023

No

Yes

03 Jun 2024

No

The main objective of the study was to evaluate If daratumumab can effectively decrease Myeloma (M) protein in subjects with intermediate or high-risk smoldering multiple myeloma (SMM) as assessed by complete response (CR) rate, and to determine if daratumumab reduced the progression or death rate in subjects with intermediate or high-risk SMM.

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.

14 Jun 2015

Yes

No

Australia: 10

Canada: 9

Germany: 6

France: 6

United Kingdom: 10

Israel: 13

Italy: 9

Netherlands: 6

Russian Federation: 7

Türkiye: 9

United States: 38

123

27

0

0

0

0

0

0

71

52

0

Overall Study (overall period)

Randomised - controlled

Yes

Daratumumab

JNJ-54767414

Injection

Subcutaneous use

Subjects in EP received daratumumab 1800 mg SC dose Q8W up to maximum of 91.6 months.

Daratumumab

JNJ-54767414

Injection

Infusion

Daratumumab 16 mg/kg was administered as IV infusion Q1W in Cycle 1 , Q2W in Cycle 2 and Cycle 3, Q4W in Cycle 4 to Cycle 7, and on Day 1 from Cycle 8 to Cycle 20. In extension phase, subjects continued to receive daratumumab IV (Q8W) after end of Cycle 20 up to 91.6 months, then completed end of treatment visit 4 weeks after last dose.

daratumumab

JNJ-54767414

Injection

Subcutaneous use

Subjects in EP received daratumumab 1800 mg SC dose Q8W up to maximum of 91.6 months.

Daratumumab

JNJ-54767414

Injection

Infusion

Daratumumab 16 mg/kg was administered as IV infusion Q1W in Cycle 1 , Q2W in Cycle 2 and Cycle 3, Q4W in Cycle 4 to Cycle 7, and on Day 1 from Cycle 8 to Cycle 20. In extension phase, subjects continued to receive daratumumab IV (Q8W) after end of Cycle 20 up to 91.6 months, then completed end of treatment visit 4 weeks after last dose.

Daratumumab

JNJ-54767414

Injection

Infusion

Daratumumab 16 mg/kg was administered as IV infusion Q1W (Day 1, 8, 15, 22, 29, 36, 43 and 50) in Cycle 1 alone.

Arm A (Long Intense)

Arm B (Intermediate)

Arm C (Short Intense)

Arm A (Long Intense)

Arm B (Intermediate)

Arm C (Short Intense)

Percentage of subjects who achieved a CR by IMWG Criteria were reported. CR was defined as CR plus 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 (PCs) in bone marrow; Stringent complete Response (sCR) was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. Response evaluable analysis set included subjects who had measurable disease at baseline as per IMWG criteria (serum and urine, serum only, urine only, FLC) and received at least 1 dose of daratumumab treatment and had at least 1 post-baseline disease assessment.

Primary

From Cycle 1 Day 1 up to 6 months post randomisation of the last subject (up to 1.58 years)

Progressive Disease per Death (PD/Death) rate were reported. PD/Death rate per patient-year was defined as number of events (PD or death) per total progression-free survival for all subjects. Intent-to-treat (ITT) analysis set was defined as subjects who have been randomly assigned to one of the 3 daratumumab schedules based on interactive web response system (IWRS).

Primary

From Cycle 1 Day 1 up to 12 months post randomisation of the last subject (up to 2.07 years)

MRD negative rate were reported. The MRD negativity rate was defined as the percentage of subjects 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 randomisation and prior to progressive disease, subsequent therapy. Intent-to-treat (ITT) analysis set was defined as subjects who have been randomly assigned to one of the 3 daratumumab schedules based on interactive web response system (IWRS).

Secondary

From Cycle 1 Day 1 up to 91.6 months

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. Intent-to-treat (ITT) analysis set was defined as subjects who have been randomly assigned to one of the 3 daratumumab schedules based on interactive web response system (IWRS). Here "N" (overall number of subjects analysed) signifies the subjects that were evaluable for this endpoint. Here, 99999 signifies that median and 90% CI were not estimable due to low number of subjects with events.

Secondary

From randomisation (Day -5) up to the date of first subsequent antimyeloma treatment (up to 7.89 years)

Per IMWG criteria, CR: was defined as a negative immunofixation on serum & urine, & <5 % PCs in bone marrow; sCR: CR plus normal FLC ratio, & absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. VGPR: Serum & urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >=50 % reduction of serum M-protein & reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if serum & urine M-protein are not measurable, a decrease of >=50% in difference between involved & uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein are not measurable and serum free light assay was also not measurable, >=50% reduction in bone marrow PCs was required in place of M-protein, provided baseline bone marrow PC percentage was >=30%. Response evaluable analysis set was used.

Secondary

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)

PFS: time from dates of randomization to initial documented PD per Sixty, 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 % >=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. ITT analysis set was used. Here, "N" (overall number of subjects analysed) signifies subjects evaluable & 99999 signifies upper limit of 90% CI were not estimable due to low number of subjects with events.

Secondary

From randomisation (Day -5) until disease progression or death whichever occurred first (up to 7.89 years)

Percentage of subjects 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, subjects progressed to symptomatic multiple myeloma (SymT MM) with stage III (S beta2M>= 5.5 mg/L) of ISS, Subjects progressed to SymT MM with adverse cytogenetic characteristics (ACC), Subjects 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. ITT analysis set was used.

Secondary

From start of treatment (Cycle 1 Day 1) until PD or prior to any subsequent anti-Multiple myeloma therapy (up to 7.89 years)

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. Intent-to-treat (ITT) analysis set was defined as subjects who have been randomly assigned to one of the 3 daratumumab schedules based on interactive web response system (IWRS). Here, 99999 signifies that median and 90% CI were not estimable due to low number of subjects with events.

Secondary

From randomisation (Day -5) till death (up to 7.89 years)

Response (IMWG Criteria) to first subsequent MM treatment: sCR: CR + normal FLC ratio & absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR:a negative immunofixation on serum & urine, & <5% PCs in BM; VGPR: Serum & urine M-protein (SMP & UMP) detectable by immunofixation but not on electrophoresis or >=90% reduction in SMP + UMP level <100mg/24 hours; PR:>=50% reduction of SMP & >=90% reduction in UMP in 24 hour or to <200 mg/24 hours; if SMP & UMP are not measurable, a decrease of >=50% difference between involved & uninvolved FLC levels was required instead of M-protein criteria. If SMP & UMP & serum free light assay was also not measurable, >=50% reduction in BM PCs was required instead of M-protein, provided baseline BM PC percentage was >=30%. ITT analysis set was used. Here "N" (overall number of subjects analysed) signifies subjects evaluable for this endpoint. Only those who received first line of therapy were analysed.

Secondary

From Cycle 1 Day 1 up to 7.89 years

All Cause Mortality: From randomisation (Day -5) up to 7.89 years; Serious Adverse Events and Other Adverse Events: From Cycle 1 Day 1 up to 7.89 years

Safety analysis set included subjects who had received at least 1 administration of daratumumab (partial or complete).

25.1

Arm A (Long Intense)

Arm B (Intermediate)

Arm C (Short Intense)