Multiple Myeloma Clinical Trial
Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
Summary
The purpose of this study is to compare the efficacy (rate of very good partial response [VGPR] or better as best response as defined by the International Myeloma Working Group [IMWG] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
Full Description
For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.
Eligibility Criteria
Inclusion Criteria:
Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to daratumumab-containing therapy with response duration of at least 4 months
Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days after cessation of treatment
Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day [mg/day] for 4 days) would not be considered prior lines of therapy
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
Exclusion Criteria:
Previous treatment with daratumumab within the last 3 months prior to randomization
Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)
History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count <350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
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There are 105 Locations for this study
Gilbert Arizona, 85234, United States
Tucson Arizona, 85745, United States
Whittier California, 90603, United States
Fort Wayne Indiana, 46804, United States
Detroit Michigan, 48201, United States
Rochester Minnesota, 55905, United States
Saint Louis Missouri, 63110, United States
New York New York, 10065, United States
Cleveland Ohio, 44195, United States
Dallas Texas, 75246, United States
Houston Texas, 77090, United States
Antwerpen , 2060, Belgium
Gent , 9000, Belgium
Campinas , 13083, Brazil
Curitiba , 81520, Brazil
Goiânia , 74605, Brazil
Natal , 59062, Brazil
Porto Alegre , 90050, Brazil
Rio de Janeiro , 20230, Brazil
Rio de Janeiro , 22775, Brazil
Salvador , 41253, Brazil
Salvador , 45995, Brazil
Sao Paulo , 01236, Brazil
Sao Paulo , 01509, Brazil
Sao Paulo , 03102, Brazil
São Paulo , 01321, Brazil
São Paulo , 01455, Brazil
Calgary Alberta, T2N 4, Canada
Aarhus N , DK-82, Denmark
Holstebro , 7500, Denmark
Odense , 5000, Denmark
Vejle , DK-71, Denmark
Lille , 59037, France
Montpellier , 34295, France
Mulhouse , 68100, France
Nantes , 44035, France
Paris , 75012, France
Paris , 75013, France
Paris , 75743, France
Pessac , 33600, France
Pierre Benite , 69310, France
Poitiers , 86021, France
Rennes Cedex , 35033, France
Toulouse , 31052, France
Tours , 37044, France
Vandoeuvre Les Nancy , 54511, France
Dresden , 1307, Germany
Essen , 45239, Germany
Essen , D-451, Germany
Hamburg , 20246, Germany
Hamm , 59075, Germany
Koblenz , 56068, Germany
Koeln , 50397, Germany
Mainz , 55101, Germany
Saarbrucken , , Germany
Tubingen , 72076, Germany
Villingen-Schwenningen , 78052, Germany
Würzburg , 97080, Germany
Athens Attica , 115 2, Greece
Athens , 106 7, Greece
Larisa , 41110, Greece
Patra , 26500, Greece
Thessaloniki , 546 3, Greece
Bergamo , 24127, Italy
Bologna , 40138, Italy
Firenze , 50139, Italy
Genova , 16132, Italy
Genova , 16132, Italy
Legnano , 20025, Italy
Meldola , 47014, Italy
Milano , 20162, Italy
Novara , 28100, Italy
Palermo , 90146, Italy
Palermo , 90146, Italy
Pavia , 27100, Italy
Roma , 00133, Italy
Roma , 00161, Italy
Roma , 30 - , Italy
Rome , 00168, Italy
San Giovanni Rotondo , 71013, Italy
Terni , 5100, Italy
Dordrecht , 3318 , Netherlands
Sittard , 6130 , Netherlands
Bydgoszcz , 85-16, Poland
Opole , 45-06, Poland
Warszawa , 01-74, Poland
Wroclaw , 50-36, Poland
Dzerzhinsk , 60601, Russian Federation
Moscow , 12528, Russian Federation
Nizhny Novgorod , 60312, Russian Federation
Ryazan , 39000, Russian Federation
Sochi , 35405, Russian Federation
St-Petersburg , 19102, Russian Federation
Syktyvkar , 16790, Russian Federation
Barcelona , 08036, Spain
Barcelona , 08908, Spain
Jerez de la Frontera , 11407, Spain
Leon , 24080, Spain
Madrid , 28034, Spain
Madrid , 28041, Spain
Madrid , 28046, Spain
Malaga , 29603, Spain
Palma , 7120, Spain
Pamplona , 31008, Spain
Salamanca , 37007, Spain
San Cristóbal de La Laguna , 38320, Spain
Sevilla , 41013, Spain
Toledo , 45007, Spain
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