Clinical trial NCT03901963: 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
Official title: A Randomized Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: 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)
timeFrame: From randomization up to 12 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization to either disease progression or death (up to 7.1 years)
measure: Percentage of Participants Who Achieved Overall MRD (at 10^-5) Negativity Conversion From Baseline to End of Study Treatment Period
timeFrame: 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)
measure: Percentage of Participants Who Achieved Durable (Greater Than or Equal to [>=] 12 Months) MRD Negative Status (10^-5)
timeFrame: 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)
measure: Response Rates by International Myeloma Working Group (IMWG) 2016 Criteria
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From randomization up to 7.1 years
measure: Duration of Complete Response (CR)
timeFrame: 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)
measure: 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)
timeFrame: From baseline (Cycle 1 Day 1) up to 7.1 years
measure: Health-related Quality of Life: Change From Baseline in European Quality of Life Five Dimensions Questionnaire-5-level (EQ-5D-5L)
timeFrame: From baseline (Cycle 1 Day 1) up to 7.1 years
measure: 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)
timeFrame: From baseline (Cycle 1 Day 1) up to 7.1 years
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Glendale
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Goodyear
country: United States
facility: Cancer Treatment Center of America Phoenix
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Fort Collins
country: United States
facility: University of Colorado Health
state: Colorado
city: New Haven
country: United States
facility: Yale University Medical Center
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Athens
country: United States
facility: University Cancer And Blood Center LLC
state: Georgia
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Zion
country: United States
facility: Cancer Treatment Centers of America
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Franciscan Health
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer And Hematology Centers of Western Michigan PC
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: HCA MidAmerica Division Inc Research Medical Center
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group/MD Anderson Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ)
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Bronx
country: United States
facility: Montefiore Einstein Center for Cancer Care
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: Mineola
country: United States
facility: NYU Winthrop
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Oncology Research Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists PC
state: Oregon
city: Portland
country: United States
facility: Oregon Health And Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital/McGlinn Cancer Institute
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Health Services
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology P A
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology P A
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Center (UT Health San Antonio)
state: Texas
city: Tyler
country: United States
facility: Texas Oncology P A
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Healthcare System
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec Universite Laval Hopital de l Enfant Jesus
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Swan D, Henderson R, McEllistrim C, Naicker SD, Quinn J, Cahill MR, Mykytiv V, Lenihan E, Mulvaney E, Nolan M, Parker I, Natoni A, Lynch K, Ryan AE, Szegezdi E, Krawczyk J, Murphy P, O'Dwyer M. CyBorD-DARA in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Results from the 16-BCNI-001/CTRIAL-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):847-852. doi: 10.1016/j.clml.2022.07.011. Epub 2022 Jul 21.