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
82
2
80.2
2.6
0

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 Disease Intervention/Treatment Phase
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 :
Dec 31, 2025

Arms and Interventions

Arm Intervention/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

    Site City State Country Postal Code
    1 University of Alabama Birmingham Birmingham Alabama United States 35294
    2 Arizona Oncology Associates, PC - HAL Glendale Arizona United States 85308
    3 Cancer Treatment Center of America, Phoenix Goodyear Arizona United States 85338
    4 University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center La Jolla California United States 92093
    5 UCLA David Geffen School of Medicine Los Angeles California United States 90095
    6 University of California San Francisco San Francisco California United States 94143
    7 Colorado Blood Cancer Institute Denver Colorado United States 80218
    8 Rocky Mountain Cancer Centers Denver Colorado United States 80218
    9 University of Colorado Health Fort Collins Colorado United States 80528
    10 Yale University Medical Center New Haven Connecticut United States 06510
    11 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    12 Cancer Specialists of North Florida Jacksonville Florida United States 32256
    13 University of Miami Leonard M. Miller School of Medicine - Sylvester Comprehensive Cancer Center Miami Florida United States 33136-1002
    14 University of Miami/Sylvester Cancer Center Miami Florida United States 33136
    15 Miami Cancer Institute Miami Florida United States 33176
    16 Moffitt Cancer Center Tampa Florida United States 33612
    17 Cleveland Clinic Florida Weston Florida United States 33331
    18 University Cancer & Blood Center, LLC Athens Georgia United States 30607
    19 Northside Hospital - Northside Hospital Cancer Institute Atlanta Georgia United States 30342-1606
    20 Georgia Cancer Center Augusta Georgia United States 30912
    21 Illinois Cancer Specialists Niles Illinois United States 60714
    22 Cancer Treatment Centers of America Zion Illinois United States 60099
    23 Fort Wayne Medical Oncology and Hematology, Inc. Fort Wayne Indiana United States 46804
    24 Franciscan Health Indianapolis Indiana United States 46237-8601
    25 University of Iowa Hospitals & Clinics Iowa City Iowa United States 52242
    26 University of Kansas Cancer Center Westwood Kansas United States 66160
    27 Norton Cancer Institute Louisville Kentucky United States 40207
    28 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    29 University of Maryland, Greenebaum Cancer Center Baltimore Maryland United States 21201
    30 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    31 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
    32 Henry Ford Cancer Institute Detroit Michigan United States 48202-2608
    33 Cancer & Hematology Centers of Western Michigan, PC Grand Rapids Michigan United States 49503
    34 Mayo Clinic Rochester Minnesota United States 55905
    35 University of Mississippi Medical Center Jackson Mississippi United States 39216
    36 Sarah Cannon Cancer Institute Kansas City Missouri United States 64132
    37 Washington University Saint Louis Missouri United States 63110
    38 Summit Medical Group/MD Anderson Cancer Center Florham Park New Jersey United States 07932
    39 Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ) New Brunswick New Jersey United States 08901-1914
    40 New York Oncology Hematology Albany New York United States 12206
    41 Montefiore Einstein Center for Cancer Care Bronx New York United States 10467
    42 Northwell Health Lake Success New York United States 11042
    43 NYU Winthrop Mineola New York United States 11501
    44 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    45 Columbia University Medical Center New York New York United States 10032
    46 University of Rochester Medical Center Rochester New York United States 14642
    47 SUNY Upstate Medical University Syracuse New York United States 13210
    48 University of North Carolina Chapel Hill North Carolina United States 27599-7305
    49 Levine Cancer Institute, Carolinas HealthCare System Charlotte North Carolina United States 28204
    50 Novant Health Charlotte North Carolina United States 28204
    51 Novant Oncology Research Institute Winston-Salem North Carolina United States 27103
    52 Wake Forest Health Sciences Winston-Salem North Carolina United States 27157
    53 Oncology Hematology Care Cincinnati Ohio United States 45236
    54 Northwest Cancer Specialists PC Portland Oregon United States 97227
    55 Oregon Health & Science University Portland Oregon United States 97239
    56 Thomas Jefferson University Philadelphia Pennsylvania United States 19107-4215
    57 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    58 West Penn Hospital Pittsburgh Pennsylvania United States 15224
    59 University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Pittsburgh Pennsylvania United States 15323
    60 Reading Hospital/McGlinn Cancer Institute West Reading Pennsylvania United States 19611
    61 Greenville Health System Cancer Institute Greenville South Carolina United States 29615-4816
    62 Spartanburg Regional Health Services Spartanburg South Carolina United States 29303
    63 Tennessee Oncology Chattanooga Tennessee United States 37404
    64 Baptist Cancer Center Memphis Tennessee United States 38120
    65 Tennessee Oncology Nashville Tennessee United States 37203
    66 Vanderbilt University Nashville Tennessee United States 37203
    67 Texas Oncology P.A. Austin Texas United States 78705
    68 Texas Oncology P.A. Dallas Texas United States 75246
    69 UT Southwestern Medical Center Dallas Texas United States 75390-8565
    70 MD Anderson Cancer Center Houston Texas United States 77030
    71 Mays Cancer Center (UT Health San Antonio) San Antonio Texas United States 78229
    72 Texas Oncology P.A. Tyler Texas United States 75702
    73 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    74 University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic Charlottesville Virginia United States 22903
    75 Virginia Cancer Specialists Gainesville Virginia United States 20155
    76 Virginia Oncology Associates Norfolk Virginia United States 23502
    77 VA Puget Sound Healthcare System Seattle Washington United States 98108
    78 University of Washington Seattle Washington United States 98109
    79 Cancer Care Northwest Spokane Washington United States 99216
    80 Princess Margaret Hospital Toronto Ontario Canada M5G 1X6
    81 McGill University Health Centre Montreal Quebec Canada H4A 3J1
    82 CHU de Québec-Université Laval-Hôpital de l'Enfant-Jésus Quebec Canada G1R 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

    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:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    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 Aug 12, 2022