Multiple Myeloma Clinical Trial
A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
Summary
The purpose of this study to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.
Full Description
This study will evaluate participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. The data available from other available studies suggests that addition of daratumumab with Velcade (bortezomib), lenalidomide, and dexamethasone [VRd] is anticipated to improve the response rates and the depth of response and may lead to improved long-term outcomes in newly diagnosed participants with MM. Daratumumab targets CD38, a protein expressed on the surface of MM cells and other hematopoietic cells. Bortezomib is a proteasome inhibitor, which plays a critical role in the pathogenesis of MM. Lenalidomide has cytotoxic effects on myeloma cells and is capable of inducing apoptosis, or programmed cell death and dexamethasone induces apoptosis in MM cells. The rationale for the study is to utilize the subcutaneous (SC) formulation of daratumumab instead of the intravenous (IV) formulation, which is expected to provide similar exposure and is expected to limit additional toxicity to participants, treated with this quadruplet regimen. The study will consist of 3 phases: Screening (up to 28 days before randomization), Treatment phase (from Cycle 1 [21 days] Day 1 and continues until disease progression) and Follow up (Postintervention). Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. Participants will undergo procedures like electrocardiogram (ECG), chest x-rays or full dose chest CT scans, Pulmonary function test (PFT), spirometry etc. during the course of study. Participants will also be monitored closely for adverse events (AEs), laboratory abnormalities, and clinical response. The duration of the study will be approximately 6.5 years.
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria Monoclonal plasma cells in the bone marrow greater than or equal to (>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria. CRAB criteria: 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); Renal insufficiency: creatinine clearance less than (<) 40 milliliter per minute (mL/min) or serum creatinine >177 micro millimoles per liter (umol/L) (>2 mg/dL); Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.
Biomarkers of Malignancy: Clonal bone marrow plasma cell percentage >=60%; Involved: uninvolved serum free light chain (FLC) ratio >=100; >1 focal lesion on magnetic resonance imaging (MRI) studies
Must have measurable disease, as assessed by central laboratory
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen
Exclusion Criteria:
Frailty index of >=2 according to Myeloma Geriatric Assessment score
Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg dexamethasone or equivalent)
Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, 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)
Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
Focal radiation therapy within 14 days of randomization with the exception of palliative radiotherapy for symptomatic pain management. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management
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There are 114 Locations for this study
Whittier California, 90805, United States
Jacksonville Florida, 32207, United States
Fort Wayne Indiana, 46804, United States
Louisville Kentucky, 40207, United States
Boston Massachusetts, 02111, United States
Boston Massachusetts, 02118, United States
Grand Rapids Michigan, 49503, United States
Kansas City Missouri, 64111, United States
New Brunswick New Jersey, 08903, United States
Farmington New Mexico, 87401, United States
Buffalo New York, 14263, United States
Mineola New York, 11501, United States
Charlotte North Carolina, 28204, United States
Cleveland Ohio, 44195, United States
Corvallis Oregon, 97330, United States
Pittsburgh Pennsylvania, 15232, United States
Spartanburg South Carolina, 29303, United States
Houston Texas, 77030, United States
Charlottesville Virginia, 22908, United States
Campinas , 13083, Brazil
Natal , 59062, Brazil
Porto Alegre , 90610, Brazil
Rio de Janeiro , 20230, Brazil
Rio de Janeiro , 22775, Brazil
Sao Paulo , 01236, Brazil
Sao Paulo , 03102, Brazil
São Paulo , 01323, Brazil
São Paulo , 01455, Brazil
São Paulo , 04122, Brazil
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 1, Canada
Vancouver British Columbia, V5Z 1, Canada
Halifax Nova Scotia, B3H 1, Canada
Brampton Ontario, L6R 3, Canada
London Ontario, N6A 5, Canada
Oshawa Ontario, L1G-2, Canada
Montreal Quebec, H4A 3, Canada
Quebec , G1J 1, Canada
Brno , 625 0, Czechia
Hradec Kralove , 500 0, Czechia
Ostrava , 708 5, Czechia
Plzen , 323 0, Czechia
Praha 2 , 128 0, Czechia
Creteil N/a , 94010, France
La Roche sur Yon Cedex 9 , 85925, France
Lille , 59037, France
Marseille Cedex 9 , 13009, France
Montpellier , 34295, France
Pessac cedex , 33604, France
Strasbourg , 67000, France
Toulouse cedex 9 , 31059, France
Aschaffenburg , 63739, Germany
Freiburg , 79106, Germany
Hamm , 59075, Germany
Koblenz , 56068, Germany
Leipzig , 4103, Germany
München , 81377, Germany
Tuebingen , 72076, Germany
Ashkelon , 78741, Israel
Hadera , 38100, Israel
Haifa , 31096, Israel
Haifa , 34362, Israel
Kfar Saba , 44281, Israel
Petah-Tiqva , 49100, Israel
Ramat Gan , 52621, Israel
Tel Aviv , 64239, Israel
Fukuoka , 814-0, Japan
Gifu , 503-8, Japan
Hyogo , 650-0, Japan
Kanazawa , 920-8, Japan
Kumamoto-shi , 860-0, Japan
Kyoto , 602-8, Japan
Matsumoto , 399-8, Japan
Matsuyama , 790-8, Japan
Nagoya , 467-8, Japan
Okayama , 701-1, Japan
Osaka , 543-8, Japan
Shibukawa , 377-0, Japan
Shibuya , 150-8, Japan
Amsterdam , 1081 , Netherlands
Dordrecht , 3318 , Netherlands
Rotterdam , 3015C, Netherlands
Brzozow , 36-20, Poland
Chorzów , 41-50, Poland
Gdansk , 80-21, Poland
Kielce , 25-73, Poland
Krakow , 30-50, Poland
Lublin , 20090, Poland
Poznan , 60-56, Poland
Slupsk , 76-20, Poland
Warszawa , 02-77, Poland
Warszawa , 02-78, Poland
Alcorcon , 28922, Spain
Barcelona , 08003, Spain
Guadalajara , 19002, Spain
Majadahonda , 28222, Spain
Pozuelo De Alarcon, Madrid , 28223, Spain
Terrassa , 08221, Spain
Ankara , 06010, Turkey
Ankara , 06100, Turkey
Ankara , 06200, Turkey
Ankara , 06590, Turkey
Istanbul , 34093, Turkey
Izmir , 35340, Turkey
Samsun , 55280, Turkey
Airdrie , ML6 0, United Kingdom
Blackpool , FY3 8, United Kingdom
Cardiff , CF14 , United Kingdom
Colchester , CO4 5, United Kingdom
Leicester , LE1 5, United Kingdom
Londonderry , BT47 , United Kingdom
Manchester , M8 6R, United Kingdom
Plymouth , PL6 8, United Kingdom
Wolverhampton , WV10 , United Kingdom
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