Multiple Myeloma Clinical Trial
Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma
Summary
The purpose of this study is to compare the efficacy of daratumumab in combination with lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).
Full Description
This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with newly diagnosed multiple myeloma and who are not candidates for high dose chemotherapy and ASCT. All the eligible participants will be randomly assigned to receive either lenalidomide and dexamethasone (Rd) (Arm A) or daratumumab in combination with lenalidomide and dexamethasone (DRd) (Arm B). Daratumumab (16 milligram per kilogram [mg/kg]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (from Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 40 mg once a week for both treatment arms. Participants in both treatment arms will continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity. All participants randomized to Treatment Arm B (DRd) in this study initially received daratumumab IV formulation; however, following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator. Daratumumab subcutaneous (SC) will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study completion. Participants in Arm A who have sponsor-confirmed disease progression may have the option to receive daratumumab provided by the sponsor (in any subsequent line of therapy) in the Follow-up phase. The study consists of 3 phases: Screening Phase (within 21 days prior to the first dose administration on Day 1), Treatment Phase (Day 1 up to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, consent withdrawal, or study end, whichever occurs first). The maximum duration of study will be 7 years after last participant is randomized. Efficacy will primarily be evaluated by PFS. Participants' safety will be monitored throughout the study.
Eligibility Criteria
Inclusion Criteria:
Participant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level >=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light chain multiple myeloma without measurable disease in serum or urine (serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Participants who are newly diagnosed and not considered for high-dose chemotherapy due to: being age >=65 years; or participants less than (<) 65 years with presence of important comorbid condition(s) likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. Sponsor review and approval of participants below 65 years of age is required before randomization
Women of childbearing potential must commit to either abstain continuously from sexual intercourse or to use 2 methods of reliable birth control simultaneously as deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab
Man, who is sexually active with a woman of child-bearing potential must agree to use a latex or synthetic condom, even if he had a successful vasectomy, must agree to use an adequate contraception method as deemed appropriate by the Investigator, and must also agree to not donate sperm during the study and for 4 weeks after last dose of lenalidomide and 4 months after last dose of daratumumab
Exclusion Criteria:
Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage)
Participant has a diagnosis of Waldenström's disease, or other conditions in which IgM M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
Participant has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
Participant has had radiation therapy within 14 days of randomization
Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
Participants with known or suspected COPD must have a FEV1 test during Screening
Participant is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid [RNA] quantitation positive)
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There is 1 Location for this study
Birmingham Alabama, , United States
Mobile Alabama, , United States
Glendale Arizona, , United States
Berkeley California, , United States
Beverly Hills California, , United States
El Cajon California, , United States
Greenbrae California, , United States
Los Angeles California, , United States
Oceanside California, , United States
San Diego California, , United States
West Hills California, , United States
Whittier California, , United States
Denver Colorado, , United States
Fort Collins Colorado, , United States
Glenwood Springs Colorado, , United States
New Haven Connecticut, , United States
Norwalk Connecticut, , United States
Washington District of Columbia, , United States
Boca Raton Florida, , United States
Boynton Beach Florida, , United States
Fort Lauderdale Florida, , United States
Fort Myers Florida, , United States
Hollywood Florida, , United States
Jacksonville Florida, , United States
Lake City Florida, , United States
Saint Petersburg Florida, , United States
Weston Florida, , United States
Atlanta Georgia, , United States
Augusta Georgia, , United States
Macon Georgia, , United States
Marietta Georgia, , United States
Chicago Illinois, , United States
Niles Illinois, , United States
Fort Wayne Indiana, , United States
Iowa City Iowa, , United States
Louisville Kentucky, , United States
Lafayette Louisiana, , United States
Marrero Louisiana, , United States
Shreveport Louisiana, , United States
Annapolis Maryland, , United States
Baltimore Maryland, , United States
Frederick Maryland, , United States
Boston Massachusetts, , United States
Detroit Michigan, , United States
Duluth Minnesota, , United States
Rochester Minnesota, , United States
Kansas City Missouri, , United States
Saint Louis Missouri, , United States
Omaha Nebraska, , United States
Hooksett New Hampshire, , United States
Brick New Jersey, , United States
Hackensack New Jersey, , United States
Livingston New Jersey, , United States
Plainfield New Jersey, , United States
Somerville New Jersey, , United States
Summit New Jersey, , United States
Mineola New York, , United States
New York New York, , United States
Rochester New York, , United States
Asheboro North Carolina, , United States
Charlotte North Carolina, , United States
Pinehurst North Carolina, , United States
Winston-Salem North Carolina, , United States
Canton Ohio, , United States
Cleveland Ohio, , United States
Columbus Ohio, , United States
Bend Oregon, , United States
Bethlehem Pennsylvania, , United States
Pittsburgh Pennsylvania, , United States
Spartanburg South Carolina, , United States
Sioux Falls South Dakota, , United States
Chattanooga Tennessee, , United States
Nashville Tennessee, , United States
Arlington Texas, , United States
Edinburg Texas, , United States
Fort Sam Houston Texas, , United States
Fort Worth Texas, , United States
Houston Texas, , United States
Plano Texas, , United States
San Antonio Texas, , United States
Ogden Utah, , United States
Seattle Washington, , United States
Spokane Washington, , United States
Tacoma Washington, , United States
Box Hill , , Australia
Fitzroy , , Australia
Footscray , , Australia
Kogarah , , Australia
Kurralta Park , , Australia
Nedlands , , Australia
New South Wales , , Australia
Woodville , , Australia
Woolloongabba N/a , , Australia
Innsbruck , , Austria
Linz , , Austria
Salzburg , , Austria
Wien N/a , , Austria
Wien Wien , , Austria
Brugge , , Belgium
Brussels , , Belgium
Brussel , , Belgium
Haine-saint-paul, LA Louviere , , Belgium
Leuven , , Belgium
Liege , , Belgium
Calgary Alberta, , Canada
Toronto Ontario, , Canada
Greenfield Park Quebec, , Canada
Montreal Quebec, , Canada
Montréal Quebec, , Canada
N/a N/a , , Canada
Nova Scotia , , Canada
Quebec , , Canada
Aarhus C , , Denmark
Odense , , Denmark
Vejle , , Denmark
Amiens N/a Picardie , , France
Angers , , France
Bayonne Cedex , , France
Bretagne , , France
Caen , , France
Cergy Pontoise , , France
Chalons Sur Saone , , France
Clermont-Ferrand , , France
Creteil , , France
Dijon , , France
Dunkerque Cedex 1 , , France
Grenoble Cedex 9 , , France
La Roche sur Yon Cedex 9 , , France
Le Chesnay Cedex , , France
Le Mans , , France
Lille Cedex , , France
Lille , , France
Limoges , , France
Lyon, Pierre-Benite , , France
Marseille Cedex 9 , , France
Metz-Tessy , , France
Montivilliers , , France
Montpellier , , France
Mulhouse , , France
Nantes , , France
Nice N/a , , France
Paris Cedex 12 , , France
Paris, 75 , , France
Paris , , France
PERIGUEUX cedex , , France
Perpignan , , France
Pessac , , France
Poitiers , , France
Reims , , France
Rennes , , France
Rouen Cedex , , France
Saint Brieuc Cedex 1 , , France
Saint Priest en Jarez , , France
St Malo Cedex , , France
St Quentin Cedex , , France
Strasbourg , , France
Toulouse Cedex 9 , , France
TOURS Cedex 9 , , France
Vandoeuvre Les Nancy , , France
Aschaffenburg , , Germany
Bad Berka , , Germany
Bonn , , Germany
Braunschweig , , Germany
Dresden , , Germany
Essen , , Germany
Frankfurt , , Germany
Hannover , , Germany
Heidelberg , , Germany
Hessen , , Germany
Kiel , , Germany
Koblenz , , Germany
Mainz , , Germany
Mannheim , , Germany
Rostock , , Germany
Schwerin , , Germany
Stuttgart , , Germany
Tuebingen , , Germany
Ulm , , Germany
Villingen-Schwenningen , , Germany
Dublin , , Ireland
Galway , , Ireland
Hadera , , Israel
Haifa , , Israel
Jerusalem , , Israel
Nahariya , , Israel
Petah Tikva , , Israel
Tel-Aviv , , Israel
Hilversum , , Netherlands
Hoofddorp , , Netherlands
Rotterdam , , Netherlands
Tilburg , , Netherlands
Falun , , Sweden
Göteborg , , Sweden
Halmstad , , Sweden
Helsingborg , , Sweden
Huddinge , , Sweden
Lulea , , Sweden
Lund , , Sweden
Stockholm , , Sweden
Örebro , , Sweden
Aberdeen , , United Kingdom
Canterbury , , United Kingdom
Dundee , , United Kingdom
Leeds , , United Kingdom
London , , United Kingdom
Manchester , , United Kingdom
Nottingham , , United Kingdom
Oxford , , United Kingdom
Plymouth, Devon , , United Kingdom
Southampton , , United Kingdom
Truro , , United Kingdom
Wolverhampton , , United Kingdom
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