Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| GEN501 | Other Identifier | Janssen Research & Development, LLC | |
| DARA-GEN501 | Other Identifier | Janssen Research & Development, LLC | |
| 2007-003783-22 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Establishment of safety profile of HuMax-CD38 when given as monotherapy in participants with multiple myeloma relapsed from or refractory to at least 2 different cytoreductive therapies and without further established treatment options.
This study is conducted in two parts. In part I, participants are enrolled into cohorts at increasing dose levels. Participant safety and efficacy during part I will determine the doses used for Part II. In part II participants will be enrolled into one of two sequential treatment arms using two of the doses defined in part 1 of the study. Part II was 5 cohorts, 3 with 8 milligram per kilogram (mg/kg) and 2 with 16 mg/kg. Part I and all but the last cohort in Part II were dosed with Phase 1/ 2 drug product. The last cohort in Part II was dosed with Phase 3 drug product. Both Part I and Part II are open-label/unmasked.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation: Daratumumab | Experimental |
| |
| Dose Expansion: Daratumumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part 1: Daratumumab | Drug | First participant will receive intravenous (injection of a substance into a vein) 0.005 milligram per kilogram (mg/kg) (planned dose) infusion of daratumumab and other participants will receive different doses. The participants will receive 7 full infusions of daratumumab and 2 predose infusions every 2 weeks. The dose of daratumumab will be escalated sequentially and considering the safety and efficacy of dose in Part 1, dose for Part 2 of the study will be decided. A predose infusion of 10% of the full dose of daratumumab will be administered a day before the first 2 full infusions. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; 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 < 100mg/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 the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. |
Not provided
Inclusion criteria
Exclusion criteria
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston | Massachusetts | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37022569 | Derived | Li X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6. | |
| 32470437 | Derived | Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. doi: 10.1016/S2352-3026(20)30081-8. |
| Label | URL |
|---|---|
| Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma | View source |
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 - <4 mg/kg | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| FG001 | Part 1 - 4 mg/kg | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| FG002 | Part 1 - 8 mg/kg | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| FG003 | Part 1 - 16 mg/kg | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| FG004 | Part 1 - 24 mg/kg | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| FG005 | Part 2 - 8 mg/kg | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. |
| FG006 | Part 2 - 16 mg/kg | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 - <4 mg/kg | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2) |
|
Up to Week 28 (for Part 1) and approximately 2.5 years
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1 - <4 mg/kg | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director | Janssen Research & Development, LLC | ClinicalTrialDisclosure@its.jnj.com |
Not provided
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C556306 | daratumumab |
| D008775 | Methylprednisolone |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Part 2: Daratumumab | Drug | In Part 2, the participants will receive dose of daratumumab as determined in part 1 (16 mg/kg) of the study. Participants will receive 8 full infusions at weekly intervals followed by biweekly (every 2 weeks) infusions for 16 additional weeks and monthly infusions until disease progression or unmanageable toxicity, whichever comes first. Predose was dropped at some point in Part 2. A predose infusion of 10 mg daratumumab will be administered on the day before the first full infusion in select cohorts. |
|
|
| Methylprednisolone | Other | Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4. Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions. |
|
| Dexamethasone | Other | Participants (Part 2) will receive 20 mg dexamethasone intravenous (IV) injection pre-dose, on the first and second days after every full-dose infusions. |
|
| Up to Week 28 (for Part 1) and Week 27 (for Part 2) |
| Part 1: Time to Response | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response. | Up to Week 28 |
| Part 2: Time to Progression (TTP) | TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method. | Up to Week 27 |
| Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier | Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. | Up to Week 27 |
| Part 2: Progression-Free Survival | Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first. | Up to Week 27 |
| Part 2: Time to Response | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response. | Up to Week 27 |
| Part 2: Overall Survival | Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method. | Approximately 3 years |
| Copenhagen Ø |
| Denmark |
| Vejle | Denmark |
| Amsterdam | Netherlands |
| Utrecht | Netherlands |
| Huddinge | Sweden |
| Lund | Sweden |
| 30536810 | Derived | Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, Abraham Y, Ceulemans H, Chiu C, Vanhoof G, Usmani SZ, Plesner T, Lonial S, Nijhof I, Lokhorst HM, Mutis T, van de Donk NWCJ, Sasser AK, Casneuf T. High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action. Cytometry A. 2019 Mar;95(3):279-289. doi: 10.1002/cyto.a.23693. Epub 2018 Dec 11. |
| 29025767 | Derived | Krejcik J, Frerichs KA, Nijhof IS, van Kessel B, van Velzen JF, Bloem AC, Broekmans MEC, Zweegman S, van Meerloo J, Musters RJP, Poddighe PJ, Groen RWJ, Chiu C, Plesner T, Lokhorst HM, Sasser AK, Mutis T, van de Donk NWCJ. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab. Clin Cancer Res. 2017 Dec 15;23(24):7498-7511. doi: 10.1158/1078-0432.CCR-17-2027. Epub 2017 Oct 12. |
| 27307294 | Derived | Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016 Aug 18;128(7):959-70. doi: 10.1182/blood-2016-03-703439. Epub 2016 Jun 15. |
| 26308596 | Derived | Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26. |
| Death |
|
| Lost to Follow-up |
|
| Study Terminated By Sponsor |
|
| Progressive Disease |
|
| Other |
|
| BG001 | Part 1 - 4 mg/kg | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| BG002 | Part 1 - 8 mg/kg | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| BG003 | Part 1 - 16 mg/kg | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| BG004 | Part 1 - 24 mg/kg | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| BG005 | Part 2 - 8 mg/kg | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. |
| BG006 | Part 2 - 16 mg/kg | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| BG007 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| No. of Prior Lines of Therapy | Count of Participants | Participants |
|
| Refractory to proteasome inhibitor (PI)/immunomodulatory agent (IMiD) | Count of Participants | Participants |
|
| OG001 | Part 1: Daratumumab 4 mg/kg | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| OG002 | Part 1:Daratumumab 8 mg/kg | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| OG003 | Part 1: Daratumumab 16 mg/kg | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| OG004 | Part 1:Daratumumab 24 mg/kg | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| OG005 | Part 2: Daratumumab 8 mg/kg | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. |
| OG006 | Part 2: Daratumumab 16 mg/kg | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
|
|
| Secondary | Overall Response Rate | Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; 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 < 100mg/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 the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to Week 28 (for Part 1) and Week 27 (for Part 2) |
|
|
|
| Secondary | Part 1: Time to Response | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels. | Posted | Median | 95% Confidence Interval | months | Up to Week 28 |
|
|
|
| Secondary | Part 2: Time to Progression (TTP) | TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Up to Week 27 |
|
|
|
| Secondary | Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier | Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. | Subset of All-Treated Analysis Set included those who had overall response in Part 2. | Posted | Median | Full Range | months | Up to Week 27 |
|
|
|
| Secondary | Part 2: Progression-Free Survival | Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Up to Week 27 |
|
|
|
| Secondary | Part 2: Time to Response | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. Here 'n' (Number of Participants Analyzed) signifies number of participants analyzed at specific time point. | Posted | Mean | Standard Deviation | months | Up to Week 27 |
|
|
|
| Secondary | Part 2: Overall Survival | Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method. | All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Approximately 3 years |
|
|
|
| 7 |
| 20 |
| 19 |
| 20 |
| EG001 | Part 1 - 4 mg/kg | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | 0 | 3 | 3 | 3 |
| EG002 | Part 1 - 8 mg/kg | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | 1 | 3 | 3 | 3 |
| EG003 | Part 1 - 16 mg/kg | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | 2 | 3 | 3 | 3 |
| EG004 | Part 1 - 24 mg/kg | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | 2 | 3 | 3 | 3 |
| EG005 | Part 2 - 8 mg/kg | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | 12 | 30 | 30 | 30 |
| EG006 | Part 2 - 16 mg/kg | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | 16 | 42 | 41 | 42 |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Atrial Flutter | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Chest Pain | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hepatic Function Abnormal | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Cytokine Release Syndrome | Immune system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bacterial Sepsis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Herpes Zoster | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Metapneumovirus Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Respiratory Syncytial Virus Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Limb Traumatic Amputation | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Spinal Compression Fracture | Injury, poisoning and procedural complications | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Blood Creatinine Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Crossmatch Incompatible | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Free Haemoglobin Present | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| International Normalised Ratio Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Osteoporotic Fracture | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Plasmacytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Amnesia | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Transient Ischaemic Attack | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Vith Nerve Paralysis | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Haemolysis | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Monocytopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Supraventricular Extrasystoles | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Ocular Hyperaemia | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Vision Blurred | Eye disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Aphthous Stomatitis | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Lip Oedema | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Mouth Ulceration | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Chest Discomfort | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Chest Pain | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hepatic Function Abnormal | Hepatobiliary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Cytokine Release Syndrome | Immune system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Herpes Zoster | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Oral Candidiasis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Viral Infection | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Vulvovaginal Candidiasis | Infections and infestations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Blood Creatine Phosphokinase Increased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Electrocardiogram QT Prolonged | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Free Haemoglobin Present | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Haptoglobin Decreased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Lymphocyte Count Decreased | Investigations | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Enzyme Abnormality | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Kyphosis | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Basal Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Benign Neoplasm of Skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Renal Impairment | Renal and urinary disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Prostatitis | Reproductive system and breast disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Laryngitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Throat Tightness | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Eczema Asteatotic | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version 18.0 | Non-systematic Assessment |
|
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| Time to best response |
|
| Time to best response |
|
|
| Time to VGPR or better response |
|
|