TriangleNCT01985126 · CITED IN SOURCE DOCUMENTS
An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2018-06-25
The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor \[PI\] and immunomodulatory drug \[IMiD\]) or are double refractory to a PI and an IMiD.
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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
Percentage of Participants With Overall Response
Duration of Response
Overall Survival
Percentage of Participants With Clinical Benefit
Time to Response
Progression Free Survival
Time to Disease Progression
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Documented multiple myeloma according to protocol-defined criteria * Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria * Eastern Cooperative Oncology Group performance status score of 0, 1, or 2 * Laboratory values and electrocardiogram within protocol-defined parameters at screening Exclusion Criteria: * Received daratumumab or other anti-CD38 therapies previously * Nonsecretory multiple myeloma * Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks * Exhibiting clinical signs of meningeal involvement of multiple myeloma * Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years * Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C * Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
- intervention Names
- Drug: Daratumumab 16 mg/kg (Part 1)
- Drug: Daratumumab 8 mg/kg (Part 1)
- Drug: Methylprednisolone
- Drug: Acetaminophen
- Drug: Diphenhydramine
- label
- Part 1
- type
- EXPERIMENTAL
- description
- Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
- intervention Names
- Drug: Methylprednisolone
- Drug: Acetaminophen
- Drug: Diphenhydramine
- Drug: Daratumumab (Part 2)
- label
- Part 2
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Part 1
- description
- Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion
- name
- Daratumumab 16 mg/kg (Part 1)
- type
- DRUG
- arm Group Labels
- Part 1
- description
- Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion
- name
- Daratumumab 8 mg/kg (Part 1)
- type
- DRUG
- arm Group Labels
- Part 1
- Part 2
- description
- Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted
- name
- Methylprednisolone
- type
- DRUG
- arm Group Labels
- Part 1
- Part 2
- description
- 650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
- name
- Acetaminophen
- type
- DRUG
- arm Group Labels
- Part 1
- Part 2
- description
- 25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.
- name
- Diphenhydramine
- type
- DRUG
- arm Group Labels
- Part 2
- description
- Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.
- name
- Daratumumab (Part 2)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 124
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Percentage of Participants With Overall Response
- time Frame
- Up to 14.4 Months
- secondary Outcomes
- description
- 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 IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be \>=0.5 g/dL) and/or; urine M-component (the absolute increase must be \>=200 mg/24 hours) and/or; 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 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL or 2.65 millimole per liter \[mmol/L\]) that can be attributed solely to the plasma cell proliferative disorder.
- measure
- Duration of Response
- time Frame
- Up to 14.4 Months
- description
- 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.
- measure
- Overall Survival
- time Frame
- Approximately up to 3 years
- description
- Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: \>=25% but \<= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.
- measure
- Percentage of Participants With Clinical Benefit
- time Frame
- Up to 14.4 Months
- description
- Time to 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).
- measure
- Time to Response
- time Frame
- Up to 14.4 Months
- description
- 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.
- measure
- Progression Free Survival
- time Frame
- Up to 14.4 Months
- description
- Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.
- measure
- Time to Disease Progression
- time Frame
- Up to 14.4 Months
Full study description
- brief Summary
- The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor \[PI\] and immunomodulatory drug \[IMiD\]) or are double refractory to a PI and an IMiD.
- detailed Description
- This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.
Source references
- references
- citation
- 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.
- pmid
- 37022569
- type
- DERIVED
- citation
- 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.
- pmid
- 32470437
- type
- DERIVED
- citation
- 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.
- pmid
- 30536810
- type
- DERIVED
- citation
- Usmani SZ, Khan I, Chiu C, Foureau D, Druhan LJ, Rigby K, Casneuf T, Sasser AK. Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. Exp Hematol Oncol. 2018 Feb 7;7:3. doi: 10.1186/s40164-018-0096-7. eCollection 2018.
- pmid
- 29445583
- type
- DERIVED
- citation
- 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.
- pmid
- 27307294
- type
- DERIVED
- citation
- Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Blade J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.
- pmid
- 26778538
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- ian time to response was 1 month (range: 0.9 to 2.8 months). The median duration of response was 13.6 months (range: 0.9+ to 14.6+ months). Monotherapy SIRIUS (NCT01985126), was an open-label trial evaluating DARZALEX monotherapy in patients with relapsed or refractory multiple myeloma who had received at least 3 prior lines of t
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Preserved source evidence · Not medical advice