A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT03901963
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD) negativity following the addition of daratumumab to lenalidomide relative to lenalidomide alone, when administered as maintenance treatment to anti-cluster of differentiation 38 (CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD positive as determined by next generation sequencing (NGS) at screening, following high-dose therapy (HDT) and autologous stem cell transplant (ASCT).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of induction therapy, have received high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) within 12 months of the start of induction therapy, and be within 6 months of ASCT on the date of randomization
- Must have a very good partial response (VGPR) or better response assessed per International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
- Must have archived bone marrow samples collected before induction treatment (that is, at diagnosis) or before transplant (for example, at the end of induction) or have existing results on the index multiple myeloma clone based on Adaptive Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD) assay. Archived bone marrow samples will be used for calibration of myeloma clonal cells to facilitate assessment of primary end point by NGS. If an existing result on index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay, as part of institutional procedures, an archived bone marrow sample is not required as long as Adaptive Biotechnologies is able to retrieve historical results on the index myeloma clone form the clinical database. Any one of the following archived samples are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube, frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment: (i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear; (iii) Please note, bone marrow core sections are not acceptable samples for analysis; (iv) In exceptional circumstances when index myeloma clone cannot be identified from the archived bone marrow sample, a post-transplant sample can be used to identify myeloma clone with permission from the sponsor
- Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS based MRD assay)
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the participant has no evidence of disease before the of 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 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
- Must not have progressed on multiple myeloma (MM) therapy at any time prior to screening
- Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management, or (c) Plasmapheresis within 28 days of randomization
- Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma
- Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
- Have known moderate or severe persistent asthma within the past 2 years or current uncontrolled asthma of any classification
- Have any of the following: (a) Known history of seropositivity for human immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, 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) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive), except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Daratumumab + Lenalidomide Daratumumab Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days. Daratumumab + Lenalidomide Lenalidomide Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days. Lenalidomide Lenalidomide Participants will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Had Minimal Residual Disease (MRD) Conversion From Baseline to 12 Months After Start of Maintenance Treatment as Determined by Next Generation Sequencing (NGS) From randomization up to 12 months Percentage of participants who achieved MRD negative (MRD conversion) status from baseline to 12 months after maintenance treatment was defined as percentage of participants who were MRD positive at baseline (randomization) and achieved MRD negative status (at 10\^-5) during the time period from randomization to 12 months plus 2 months window, but prior to progressive disease (PD) and subsequent anti-myeloma therapy.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) From randomization to either disease progression or death (up to 7.1 years) Percentage of Participants Who Achieved Overall MRD (at 10^-5) Negativity Conversion From Baseline to End of Study Treatment Period From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years) Percentage of Participants Who Achieved Durable (Greater Than or Equal to [>=] 12 Months) MRD Negative Status (10^-5) From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years) Response Rates by International Myeloma Working Group (IMWG) 2016 Criteria From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years) Overall Survival (OS) From randomization up to 7.1 years Duration of Complete Response (CR) From date of initial documentation of CR or sCR up to first documented disease progression or death due to disease progression whichever occurs first (up to 7.1 years) Health-related Quality of Life: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-C30 (EORTC QLQ-C30) From baseline (Cycle 1 Day 1) up to 7.1 years Health-related Quality of Life: Change From Baseline in European Quality of Life Five Dimensions Questionnaire-5-level (EQ-5D-5L) From baseline (Cycle 1 Day 1) up to 7.1 years Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Cycle 1 Day 1 up to 30 days after the last study treatment or day prior to start of subsequent antimyeloma therapy (up to 7.1 years) Health-related Quality of Life: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Multiple Myeloma Module (EORTC QLQ-MY20) From baseline (Cycle 1 Day 1) up to 7.1 years
Trial Locations
- Locations (70)
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Oncology Associates, PC - HAL
🇺🇸Glendale, Arizona, United States
Cancer Treatment Center of America Phoenix
🇺🇸Goodyear, Arizona, United States
University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center
🇺🇸La Jolla, California, United States
UCLA David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
University of Colorado Health
🇺🇸Fort Collins, Colorado, United States
Yale University Medical Center
🇺🇸New Haven, Connecticut, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
University of Miami Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
University Cancer And Blood Center LLC
🇺🇸Athens, Georgia, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Cancer Treatment Centers of America
🇺🇸Zion, Illinois, United States
Fort Wayne Medical Oncology and Hematology, Inc.
🇺🇸Fort Wayne, Indiana, United States
Franciscan Health
🇺🇸Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
Cancer And Hematology Centers of Western Michigan PC
🇺🇸Grand Rapids, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
HCA MidAmerica Division Inc Research Medical Center
🇺🇸Kansas City, Missouri, United States
Summit Medical Group/MD Anderson Cancer Center
🇺🇸Florham Park, New Jersey, United States
Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ)
🇺🇸New Brunswick, New Jersey, United States
New York Oncology Hematology
🇺🇸Albany, New York, United States
Montefiore Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Northwell Health
🇺🇸Lake Success, New York, United States
NYU Winthrop
🇺🇸Mineola, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Levine Cancer Institute, Carolinas HealthCare System
🇺🇸Charlotte, North Carolina, United States
Novant Health
🇺🇸Charlotte, North Carolina, United States
Novant Oncology Research Institute
🇺🇸Winston-Salem, North Carolina, United States
Wake Forest Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Northwest Cancer Specialists PC
🇺🇸Portland, Oregon, United States
Oregon Health And Science University
🇺🇸Portland, Oregon, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Reading Hospital/McGlinn Cancer Institute
🇺🇸West Reading, Pennsylvania, United States
Greenville Health System Cancer Institute
🇺🇸Greenville, South Carolina, United States
Spartanburg Regional Health Services
🇺🇸Spartanburg, South Carolina, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Texas Oncology P A
🇺🇸Tyler, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Mays Cancer Center (UT Health San Antonio)
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
VA Puget Sound Healthcare System
🇺🇸Seattle, Washington, United States
University of Washington
🇺🇸Seattle, Washington, United States
Cancer Care Northwest
🇺🇸Spokane, Washington, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
CHU de Quebec Universite Laval Hopital de l Enfant Jesus
🇨🇦Quebec, Canada