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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 (AURIGA)

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ClinicalTrials.gov Identifier: NCT03901963
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: Lenalidomide Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 26, 2019
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : August 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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 Name: 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.




Primary Outcome Measures :
  1. Percentage of Participants with Minimal Residual Disease (MRD) Negative Status as determined by NGS [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03901963


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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United States, Alabama
University of Alabama Birmingham Recruiting
Birmingham, Alabama, United States, 35294
United States, Arizona
Arizona Oncology Associates, PC - HAL Recruiting
Glendale, Arizona, United States, 85308
Cancer Treatment Center of America, Phoenix Not yet recruiting
Goodyear, Arizona, United States, 85338
United States, California
University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
UCLA David Geffen School of Medicine Recruiting
Los Angeles, California, United States, 90095
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Rocky Mountain Cancer Centers Recruiting
Denver, Colorado, United States, 80218
University of Colorado Health Recruiting
Fort Collins, Colorado, United States, 80528
United States, Connecticut
Yale University Medical Center Recruiting
New Haven, Connecticut, United States, 06510
United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Cancer Specialists of North Florida Recruiting
Jacksonville, Florida, United States, 32256
University of Miami Leonard M. Miller School of Medicine - Sylvester Comprehensive Cancer Center Withdrawn
Miami, Florida, United States, 33136-1002
University of Miami/Sylvester Cancer Center Not yet recruiting
Miami, Florida, United States, 33136
Miami Cancer Institute Recruiting
Miami, Florida, United States, 33176
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Cleveland Clinic Florida Recruiting
Weston, Florida, United States, 33331
United States, Georgia
Northside Hospital - Northside Hospital Cancer Institute Withdrawn
Atlanta, Georgia, United States, 30342-1606
United States, Illinois
Illinois Cancer Specialists Recruiting
Niles, Illinois, United States, 60714
Cancer Treatment Centers of America Not yet recruiting
Zion, Illinois, United States, 60099
United States, Indiana
Fort Wayne Medical Oncology and Hematology, Inc. Recruiting
Fort Wayne, Indiana, United States, 46804
Franciscan Health Recruiting
Indianapolis, Indiana, United States, 46237-8601
United States, Iowa
University of Iowa Hospitals & Clinics Withdrawn
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66160
United States, Kentucky
Norton Cancer Institute Completed
Louisville, Kentucky, United States, 40207
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
United States, Maryland
University of Maryland, Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Barbara Ann Karmanos Cancer Institute Withdrawn
Detroit, Michigan, United States, 48201
Henry Ford Cancer Institute Recruiting
Detroit, Michigan, United States, 48202-2608
Cancer & Hematology Centers of Western Michigan, PC Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Mayo Clinic Withdrawn
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center Recruiting
Jackson, Mississippi, United States, 39216
United States, Missouri
Sarah Cannon Cancer Institute Recruiting
Kansas City, Missouri, United States, 64132
Washington University Withdrawn
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Summit Medical Group/MD Anderson Cancer Center Recruiting
Florham Park, New Jersey, United States, 07932
Rutgers, The State Univ of NJ-Robert Wood Johnson Medical School-The Cancer Institute of NJ (CINJ) Recruiting
New Brunswick, New Jersey, United States, 08901-1914
United States, New York
New York Oncology Hematology Recruiting
Albany, New York, United States, 12206
Montefiore Einstein Center for Cancer Care Recruiting
Bronx, New York, United States, 10467
Northwell Health Recruiting
Lake Success, New York, United States, 11042
NYU Winthrop Recruiting
Mineola, New York, United States, 11501
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
University of Rochester Medical Center Withdrawn
Rochester, New York, United States, 14642
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
Levine Cancer Institute, Carolinas HealthCare System Recruiting
Charlotte, North Carolina, United States, 28204
Novant Health Recruiting
Charlotte, North Carolina, United States, 28204
Novant Oncology Research Institute Recruiting
Winston-Salem, North Carolina, United States, 27103
Wake Forest Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Oncology Hematology Care Recruiting
Cincinnati, Ohio, United States, 45236
United States, Oregon
Northwest Cancer Specialists PC Completed
Portland, Oregon, United States, 97227
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107-4215
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
West Penn Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15224
University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15323
Reading Hospital/McGlinn Cancer Institute Recruiting
West Reading, Pennsylvania, United States, 19611
United States, South Carolina
Greenville Health System Cancer Institute Recruiting
Greenville, South Carolina, United States, 29615-4816
Spartanburg Regional Health Services Recruiting
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Tennessee Oncology Completed
Chattanooga, Tennessee, United States, 37404
Baptist Cancer Center Recruiting
Memphis, Tennessee, United States, 38120
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Vanderbilt University Withdrawn
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology P.A. Recruiting
Austin, Texas, United States, 78705
Texas Oncology P.A. Recruiting
Dallas, Texas, United States, 75246
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-8565
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Mays Cancer Center (UT Health San Antonio) Not yet recruiting
San Antonio, Texas, United States, 78229
Texas Oncology P.A. Recruiting
Tyler, Texas, United States, 75702
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
United States, Virginia
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic Recruiting
Charlottesville, Virginia, United States, 22903
Virginia Cancer Specialists Recruiting
Gainesville, Virginia, United States, 20155
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
United States, Washington
VA Puget Sound Healthcare System Not yet recruiting
Seattle, Washington, United States, 98108
University of Washington Recruiting
Seattle, Washington, United States, 98109
Cancer Care Northwest Recruiting
Spokane, Washington, United States, 99216
Canada, Ontario
Princess Margaret Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 1X6
Canada, Quebec
McGill University Health Centre Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03901963    
Other Study ID Numbers: CR108599
54767414MMY3021 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Lenalidomide
Daratumumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents