Multiple Myeloma Clinical Trial
A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma
Summary
The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).
Full Description
This study consists of 3 phases: Screening Phase (up to 35 days), an Active Monitoring Phase or a Treatment Phase of 39 cycles or 36 months (whichever occurs first), and a Follow-up Phase which will continue until death, lost to follow-up, consent withdrawal, or study end (approximately 8 years after the first participant is randomized), whichever occurs first. Active monitoring cycles and treatment cycles are 4 weeks in length. For all participants, disease evaluations will be performed every 12 weeks until confirmed progressive disease (PD). After PD, survival is to be followed at least every 6 months, until the end of the study. Participants will undergo tumor assessments, pharmacokinetics, biomarkers and safety evaluations (adverse events, laboratory tests, vital sign measurements, physical examinations, Eastern Cooperative Oncology Group [ECOG] performance status) over the time.
Eligibility Criteria
Inclusion Criteria:
Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group [IMWG] criteria) for less than or equal to (<=) 5 years with measurable disease at the time of randomization, defined as serum M protein greater than or equal to (>=) 10 gram per liter (g/L) or urine M protein >= 200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) >=100 milligram per liter (mg/L) and abnormal serum FLC ratio
Clonal bone marrow plasma cells (BMPCs) >= 10 percentage (%); and at least 1 of the following risk factors; Serum M protein >= 30 g/L, immunoglobulin (Ig)A SMM, immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM, and IgG should be considered in determination for immunoparesis; IgD and IgE are not considered in this assessment), serum involved: uninvolved FLC ratio >= 8 and less than (<) 100, or clonal BMPCs greater than (>) 50% to <60% with measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective method of contraception
A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization
During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction
Exclusion Criteria:
Multiple myeloma (MM), requiring treatment, defined by any of the following:
Bone lesions (1 or more osteolytic lesions on low-dose whole body computed tomography [LDCT], positron-emission tomography with computed tomography [PET-CT] or CT). Participants who have benign/post-traumatic bone lesions visible on screening images as well as previous imaging, may be considered for inclusion. Details (diagnosis, location, duration) on benign/post-traumatic pre-existing bone lesions that can be seen on the screening images (example [eg.], old fractures) and were also present on previous imaging are to be reported in the case report form (CRF)
Hypercalcemia (serum calcium greater than [>]0.25 millimoles per liter [mmol/L] [>1 milligram per deciliter {mg/dL}] higher than upper limit of normal [ULN] or >2.75 mmol/L [>11 mg/dL]). Participants who have clinically stable hypercalcemia attributable to a disease other than multiple myeloma (eg, hyperparathyroidism) may be considered for inclusion after a case by case review by the medical monitor
Renal insufficiency, preferably determined by creatinine clearance less than (<)40 milliliter per minute (mL/min) measured or estimated using the Modification of Diet in Renal Disease (MDRD), or serum creatinine >177 micromole per liter (μmol/L). Participants who have clinically stable renal insufficiency attributable to a disease other than multiple myeloma (eg, glomerulonephritis) may be considered for inclusion after a case by case review by the medical monitor
Anemia, defined as hemoglobin <10 gram per deciliter (g/dL) or >2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted. Participants who have clinically stable anemia attributable to a disease other than multiple myeloma (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for inclusion after a case by case review by the medical monitor
Clonal BMPC percentage >=60%
Serum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100 mg/L)
More than 1 focal lesion >=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI)
Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis
Exposure to any of the following:
Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies
Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate and denosumab as indicated for osteoporosis is acceptable
Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1
Ongoing treatment with corticosteroids with a dose >10 milligram (mg) prednisone or equivalent per day at the time of randomization; or >280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization
Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab), immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or other treatments that are likely to interfere with the study procedures or results
Received treatment (chemotherapy, surgery, et cetera [etc]) for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion), which is considered cured with minimal risk of recurrence within 3 years
Medical or psychiatric condition or disease (for example, active systemic disease [including presence of auto-antibodies], uncontrolled diabetes) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, hyaluronidase, or other human proteins, or their excipients, or known sensitivity to mammalian-derived products (including dairy allergy)
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There are 161 Locations for this study
Phoenix Arizona, 85016, United States
Whittier California, 90805, United States
Miami Florida, 33176, United States
Atlanta Georgia, 30322, United States
Iowa City Iowa, 52242, United States
Metairie Louisiana, 70006, United States
Boston Massachusetts, 02215, United States
Ann Arbor Michigan, 48109, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
North Las Vegas Nevada, 89086, United States
Albany New York, 12206, United States
Stony Brook New York, 11794, United States
Chapel Hill North Carolina, 27599, United States
Charlotte North Carolina, 28204, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43210, United States
Portland Oregon, 97239, United States
Philadelphia Pennsylvania, 19111, United States
Austin Texas, 78705, United States
Dallas Texas, 75216, United States
Tyler Texas, 75702, United States
Seattle Washington, 90805, United States
Buenos Aires , C1118, Argentina
Buenos Aires , C1199, Argentina
Ciudad de Buenos Aires , 1431, Argentina
Cordoba , X5016, Argentina
La Plata , B1900, Argentina
Rosario , 2000, Argentina
Heidelberg , 3150 , Australia
Waratah , 2298, Australia
West Perth , 6005, Australia
Woodville , 5011, Australia
Antwerpen , 2060, Belgium
Brugge , 8000, Belgium
Brussel , 1090, Belgium
Gent , 9000, Belgium
Hasselt , 3500, Belgium
Kortrijk , 8500, Belgium
Florianopolis , 88034, Brazil
Goiânia , 74605, Brazil
Joinville , 89201, Brazil
Porto Alegre , 90035, Brazil
Rio de Janeiro , 22775, Brazil
Salvador , 41235, Brazil
Sao Jose do Rio Preto , 15090, Brazil
Sao Paulo , 01236, Brazil
São Paulo , 01455, Brazil
São Paulo , 04122, Brazil
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 1, Canada
Oshawa Ontario, L1G-2, Canada
Hradec Kralove , 500 0, Czechia
Ostrava , 70852, Czechia
Plzen , 323 0, Czechia
Praha 2 , 128 0, Czechia
Aarhus N. , 8200, Denmark
Copenhagen , 2100, Denmark
Odense C , 5000, Denmark
Ålborg , 9000, Denmark
Limoges , 87000, France
Nantes cedex 01 , 44035, France
Pessac cedex , 33604, France
Pierre Benite cedex , 69495, France
Poitiers , 86021, France
Rennes , 35033, France
Tours Cedex 9 , 37044, France
Berlin , 13125, Germany
Hamm , 59073, Germany
Heidelberg , 69120, Germany
Muenster , 48149, Germany
Tübingen , 72076, Germany
Ulm , 89081, Germany
Athens Attica , 115 2, Greece
Budapest N/a , 1083, Hungary
Budapest , 1088, Hungary
Budapest , 1097, Hungary
Debrecen , 4032, Hungary
Afula , 18101, Israel
Ashkelon , 78741, Israel
Haifa , 31048, Israel
Haifa , 34362, Israel
Haifa , 35254, Israel
Jerusalem , 91120, Israel
Nahariya , 22100, Israel
Petah-Tiqva , 49100, Israel
Ramat Gan , 52621, Israel
Tel-Aviv , 64239, Israel
Bologna , 40138, Italy
Cagliari , 09121, Italy
Cuneo , 12100, Italy
Roma , 00144, Italy
Roma , 00161, Italy
Torino , 10126, Italy
Varese , 21100, Italy
Fukuoka , 814-0, Japan
Fukuyama , 720-0, Japan
Gifu , 503-8, Japan
Hyogo , 650-0, Japan
Kagoshima , 890-8, Japan
Kanazawa , 920-8, Japan
Kawachi-Nagano , 586-8, Japan
Kumamoto-shi , 860-0, Japan
Kurume , 830-0, Japan
Kyoto , 603-8, Japan
Matsumoto , 399-8, Japan
Matsuyama , 790-8, Japan
Nagoya , 467-8, Japan
Niigata , 951-8, Japan
Okayama , 701-1, Japan
Sendai-City , 983-8, Japan
Shibukawa , 377-0, Japan
Shibuya , 150-8, Japan
Aguascalientes , 20121, Mexico
Cuernavaca , 62290, Mexico
Guadalajara , 44160, Mexico
Merida , 97134, Mexico
Monterrey , 64460, Mexico
Apeldoorn , 7334 , Netherlands
Den Haag , 2545 , Netherlands
Dordrecht , 3318 , Netherlands
Tilburg , 5042 , Netherlands
Oslo , 0450, Norway
Brzozow , 36-20, Poland
Bydgoszcz , 85-16, Poland
Legnica , 59-22, Poland
Poznań , 60-84, Poland
Warszawa , 02-77, Poland
Dzerzhinsk , 60601, Russian Federation
Moscow , 12528, Russian Federation
Moscow , 12930, Russian Federation
Nizhny Novgorod , 60312, Russian Federation
Perm , 61407, Russian Federation
Petrozavodsk , 18501, Russian Federation
Ryazan , 39000, Russian Federation
St-Petersburg , 19102, Russian Federation
Syktyvkar , 16790, Russian Federation
Badalona , 08916, Spain
Barcelona , 08036, Spain
Barcelona , 8035, Spain
Madrid , 28007, Spain
Madrid , 28031, Spain
Madrid , 28034, Spain
Pamplona , 31008, Spain
Pozuelo De Alarcon, Madrid , 28223, Spain
Salamanca , 37007, Spain
Valencia , 46017, Spain
Falun , 79182, Sweden
Luelå , 97180, Sweden
Stockholm , 141 8, Sweden
Ankara , 06230, Turkey
Ankara , 6100, Turkey
Edirne , 22030, Turkey
Istanbul , 34093, Turkey
Kayseri , 38030, Turkey
Samsun , 55139, Turkey
Birmingham , B9 5S, United Kingdom
Bristol , BS2 8, United Kingdom
Canterbury , CT1 3, United Kingdom
London , EC1A , United Kingdom
Manchester , M20 4, United Kingdom
Nottingham , NG5 1, United Kingdom
Stoke-On-Trent , ST4 6, United Kingdom
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