AURIGA: 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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03901963
Collaborator
(none)
214
Enrollment
82
Locations
2
Arms
75.2
Anticipated Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
214 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 26, 2019
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Aug 1, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Daratumumab + 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.

Drug: Daratumumab
Daratumumab 1800 mg will be administered by SC injection weekly during Cycles 1 and 2, every 2 weeks during Cycles 3 through 6, and every 4 weeks from Cycle 7 onward until confirmed progressive disease (PD), unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles.
Other Names:
  • DARZALEX
  • Drug: Lenalidomide
    Lenalidomide 10 mg will be administered orally from Day 1 to Day 28 (continuously) of each 28-day cycle until confirmed PD, unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.

    Active Comparator: Lenalidomide

    Participants will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.

    Drug: Lenalidomide
    Lenalidomide 10 mg will be administered orally from Day 1 to Day 28 (continuously) of each 28-day cycle until confirmed PD, unacceptable toxicity, or until end of study treatment for a maximum of 36 cycles. After 3 cycles of maintenance therapy, if well tolerated, the lenalidomide dose may be increased to 15 mg daily, at the discretion of the investigator.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants with Minimal Residual Disease (MRD) Negative Status as determined by NGS [Up to 12 months]

      The percentage of participants with MRD negative status (at 10^[-5]), that is the MRD conversion rate from baseline to 12 months after maintenance treatment, will be determined by next generation sequencing (NGS).

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) [Up to 3 years]

      PFS: duration from date of randomization to PD/death, whichever occurs first. IMWG criteria for PD: greater than or equal to (>=)25% from lowest response level in serum M-protein (absolute increase >=0.5 gram per deciliter [g/dL]); serum M-protein increase >=1 g/dL, if lowest M component >=5 g/dL; urine M-component: absolute increase >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow PC%: absolute increase >=10%; appearance of new lesion(s), >=50% increase from nadir in sum of products of maximal perpendicular diameters of measured lesions (SPD) >1 lesion, or >=50% increase in longest diameter of previous lesion >1 centimeter (cm) in short axis; >=50% increase in circulating PCs if this is only measure of disease.

    2. Percentage of Participants with Overall Minimal Residual Disease (MRD) Negative Status [Up to 3 years]

      Percentage of participants with overall MRD negative status at any time after the date of randomization will be assessed.

    3. Durable MRD Negative Rate [Up to 3 years]

      Durable MRD negativity rate, defined as the percentage of participants who have achieved MRD negative status (at 10^-5) in 2 bone marrow aspirate examinations that are a minimum of 1 year apart, without any examination showing MRD positive status in between assessments.

    4. Percentage of Participants Achieving Complete Response (CR) or Stringent Complete Response (sCR) [Up to 3 years]

      Complete response is based on serum M-Protein assessments. International Myeloma Working Group (IMWG) criteria for CR: Negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (<) 5 percent (%) (plasma cells [PCs] in bone marrow aspirates. IMWG criteria for sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal cells in bone marrow biopsy by immunohistochemistry.

    5. Overall Survival (OS) [Up to 4.1 years]

      OS is defined as the time from the date of randomization to date of death due to any cause. If participant is alive, participant's data will be censored at the last date participant was known to be alive.

    6. Duration of Complete Response (CR) [Up to 3 years]

      Duration of CR is the duration from the date of initial documentation of a CR or sCR to the date of first documented evidence of progressive disease (PD) as per IMWG criteria, or death due to PD, whichever occurs first.

    7. Change in Health-Related Quality of Life (HRQoL) as Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 [Baseline up to 3 years]

      EORTC QLQ-C30 has been widely used among participants with multiple myeloma. It includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("past week item") and responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

    8. Change in HRQoL as Measured by European Quality of Life Five Dimensions Questionnaire-5-level (EQ-5D-5L) [Baseline up to 3 years]

      The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

    9. Change in HRQoL as Measured by EORTC QLQ-Multiple Myeloma Module (MY20) [Baseline up to 3 years]

      The EORTC QLQ-MY20 has been designed to be used alongside the EORTC QLQ-C30 to address issues of more relevance to myeloma participants. The EORTC QLQ-MY20 20-items make up 4 scales: disease symptoms, side effects of treatment, future perspective, and body image. Item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

    10. Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability [Up to 4.1 years]

      An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are AEs with onset during the Treatment Phase or that are a consequence of a pre-existing condition that has worsened since baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 79 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama BirminghamBirminghamAlabamaUnited States35294
    2Arizona Oncology Associates, PC - HALGlendaleArizonaUnited States85308
    3Cancer Treatment Center of America, PhoenixGoodyearArizonaUnited States85338
    4University of California San Diego (UCSD) - The Rebecca and John Moores Cancer CenterLa JollaCaliforniaUnited States92093
    5UCLA David Geffen School of MedicineLos AngelesCaliforniaUnited States90095
    6University of California San FranciscoSan FranciscoCaliforniaUnited States94143
    7Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    8Rocky Mountain Cancer CentersDenverColoradoUnited States80218
    9University of Colorado HealthFort CollinsColoradoUnited States80528
    10Yale University Medical CenterNew HavenConnecticutUnited States06510
    11MedStar Georgetown University HospitalWashingtonDistrict of ColumbiaUnited States20007
    12Cancer Specialists of North FloridaJacksonvilleFloridaUnited States32256
    13University of Miami Leonard M. Miller School of Medicine - Sylvester Comprehensive Cancer CenterMiamiFloridaUnited States33136-1002
    14University of Miami/Sylvester Cancer CenterMiamiFloridaUnited States33136
    15Miami Cancer InstituteMiamiFloridaUnited States33176
    16Moffitt Cancer CenterTampaFloridaUnited States33612
    17Cleveland Clinic FloridaWestonFloridaUnited States33331
    18University Cancer & Blood Center, LLCAthensGeorgiaUnited States30607
    19Northside Hospital - Northside Hospital Cancer InstituteAtlantaGeorgiaUnited States30342-1606
    20Georgia Cancer CenterAugustaGeorgiaUnited States30912
    21Illinois Cancer SpecialistsNilesIllinoisUnited States60714
    22Cancer Treatment Centers of AmericaZionIllinoisUnited States60099
    23Fort Wayne Medical Oncology and Hematology, Inc.Fort WayneIndianaUnited States46804
    24Franciscan HealthIndianapolisIndianaUnited States46237-8601
    25University of Iowa Hospitals & ClinicsIowa CityIowaUnited States52242
    26University of Kansas Cancer CenterWestwoodKansasUnited States66160
    27Norton Cancer InstituteLouisvilleKentuckyUnited States40207
    28Ochsner Clinic FoundationNew OrleansLouisianaUnited States70121
    29University of Maryland, Greenebaum Cancer CenterBaltimoreMarylandUnited States21201
    30Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    31Barbara Ann Karmanos Cancer InstituteDetroitMichiganUnited States48201
    32Henry Ford Cancer InstituteDetroitMichiganUnited States48202-2608
    33Cancer & Hematology Centers of Western Michigan, PCGrand RapidsMichiganUnited States49503
    34Mayo ClinicRochesterMinnesotaUnited States55905
    35University of Mississippi Medical CenterJacksonMississippiUnited States39216
    36Sarah Cannon Cancer InstituteKansas CityMissouriUnited States64132
    37Washington UniversitySaint LouisMissouriUnited States63110
    38Summit Medical Group/MD Anderson Cancer CenterFlorham ParkNew JerseyUnited States07932
    39Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ)New BrunswickNew JerseyUnited States08901-1914
    40New York Oncology HematologyAlbanyNew YorkUnited States12206
    41Montefiore Einstein Center for Cancer CareBronxNew YorkUnited States10467
    42Northwell HealthLake SuccessNew YorkUnited States11042
    43NYU WinthropMineolaNew YorkUnited States11501
    44Icahn School of Medicine at Mount SinaiNew YorkNew YorkUnited States10029
    45Columbia University Medical CenterNew YorkNew YorkUnited States10032
    46University of Rochester Medical CenterRochesterNew YorkUnited States14642
    47SUNY Upstate Medical UniversitySyracuseNew YorkUnited States13210
    48University of North CarolinaChapel HillNorth CarolinaUnited States27599-7305
    49Levine Cancer Institute, Carolinas HealthCare SystemCharlotteNorth CarolinaUnited States28204
    50Novant HealthCharlotteNorth CarolinaUnited States28204
    51Novant Oncology Research InstituteWinston-SalemNorth CarolinaUnited States27103
    52Wake Forest Health SciencesWinston-SalemNorth CarolinaUnited States27157
    53Oncology Hematology CareCincinnatiOhioUnited States45236
    54Northwest Cancer Specialists PCPortlandOregonUnited States97227
    55Oregon Health & Science UniversityPortlandOregonUnited States97239
    56Thomas Jefferson UniversityPhiladelphiaPennsylvaniaUnited States19107-4215
    57Fox Chase Cancer CenterPhiladelphiaPennsylvaniaUnited States19111
    58West Penn HospitalPittsburghPennsylvaniaUnited States15224
    59University of Pittsburgh Medical Center (UPMC) - Hillman Cancer CenterPittsburghPennsylvaniaUnited States15323
    60Reading Hospital/McGlinn Cancer InstituteWest ReadingPennsylvaniaUnited States19611
    61Greenville Health System Cancer InstituteGreenvilleSouth CarolinaUnited States29615-4816
    62Spartanburg Regional Health ServicesSpartanburgSouth CarolinaUnited States29303
    63Tennessee OncologyChattanoogaTennesseeUnited States37404
    64Baptist Cancer CenterMemphisTennesseeUnited States38120
    65Tennessee OncologyNashvilleTennesseeUnited States37203
    66Vanderbilt UniversityNashvilleTennesseeUnited States37203
    67Texas Oncology P.A.AustinTexasUnited States78705
    68Texas Oncology P.A.DallasTexasUnited States75246
    69UT Southwestern Medical CenterDallasTexasUnited States75390-8565
    70MD Anderson Cancer CenterHoustonTexasUnited States77030
    71Mays Cancer Center (UT Health San Antonio)San AntonioTexasUnited States78229
    72Texas Oncology P.A.TylerTexasUnited States75702
    73Huntsman Cancer InstituteSalt Lake CityUtahUnited States84112
    74University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology ClinicCharlottesvilleVirginiaUnited States22903
    75Virginia Cancer SpecialistsGainesvilleVirginiaUnited States20155
    76Virginia Oncology AssociatesNorfolkVirginiaUnited States23502
    77VA Puget Sound Healthcare SystemSeattleWashingtonUnited States98108
    78University of WashingtonSeattleWashingtonUnited States98109
    79Cancer Care NorthwestSpokaneWashingtonUnited States99216
    80Princess Margaret HospitalTorontoOntarioCanadaM5G 1X6
    81McGill University Health CentreMontrealQuebecCanadaH4A 3J1
    82CHU de Québec -L'Hôtel-Dieu de QuébecQuebecCanadaG1R 2J6

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03901963
    Other Study ID Numbers:
    • CR108599
    • 54767414MMY3021
    First Posted:
    Apr 3, 2019
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 3, 2021