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

Multiple Myeloma Clinical Trial

— AURIGA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03901963
• Other study ID #: CR108599
• Secondary ID: 54767414MMY3021
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 26, 2019
• Est. completion date: May 29, 2026

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: May 29, 2026
• Est. primary completion date: June 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasm, Residual
• Neoplasms, Plasma Cell

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montreal	Quebec
Canada	CHU de Quebec Universite Laval Hopital de l Enfant Jesus	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	New York Oncology Hematology	Albany	New York
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Texas Oncology P.A.	Austin	Texas
United States	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Montefiore Einstein Center for Cancer Care	Bronx	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	University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic	Charlottesville	Virginia
United States	Tennessee Oncology	Chattanooga	Tennessee
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Texas Oncology P.A.	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Summit Medical Group/MD Anderson Cancer Center	Florham Park	New Jersey
United States	University of Colorado Health	Fort Collins	Colorado
United States	Fort Wayne Medical Oncology and Hematology, Inc.	Fort Wayne	Indiana
United States	Virginia Cancer Specialists	Gainesville	Virginia
United States	Arizona Oncology Associates, PC - HAL	Glendale	Arizona
United States	Cancer Treatment Center of America, Phoenix	Goodyear	Arizona
United States	Cancer & Hematology Centers of Western Michigan, PC	Grand Rapids	Michigan
United States	Greenville Health System Cancer Institute	Greenville	South Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Franciscan Health	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	HCA MidAmerica Division Inc Research Medical Center	Kansas City	Missouri
United States	University of California San Diego (UCSD) - The Rebecca and John Moores Cancer Center	La Jolla	California
United States	Northwell Health	Lake Success	New York
United States	UCLA David Geffen School of Medicine	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Miami Cancer Institute	Miami	Florida
United States	University of Miami Sylvester Cancer Center	Miami	Florida
United States	NYU Winthrop	Mineola	New York
United States	Tennessee Oncology	Nashville	Tennessee
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	Yale University Medical Center	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Northwest Cancer Specialists PC	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Mays Cancer Center (UT Health San Antonio)	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	VA Puget Sound Healthcare System	Seattle	Washington
United States	Spartanburg Regional Health Services	Spartanburg	South Carolina
United States	Cancer Care Northwest	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Texas Oncology P.A.	Tyler	Texas
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Reading Hospital/McGlinn Cancer Institute	West Reading	Pennsylvania
United States	Cleveland Clinic Florida	Weston	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Novant Oncology Research Institute	Winston-Salem	North Carolina
United States	Wake Forest Health Sciences	Winston-Salem	North Carolina
United States	Cancer Treatment Centers of America	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Minimal Residual Disease (MRD) Negative Status as determined by NGS	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).	Up to 12 months
Secondary	Progression-free Survival (PFS)	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.	Up to 3 years
Secondary	Percentage of Participants with Overall Minimal Residual Disease (MRD) Negative Status	Percentage of participants with overall MRD negative status at any time after the date of randomization will be assessed.	Up to 3 years
Secondary	Durable MRD Negative Rate	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.	Up to 3 years
Secondary	Percentage of Participants Achieving Complete Response (CR) or Stringent Complete Response (sCR)	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.	Up to 3 years
Secondary	Overall Survival (OS)	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.	Up to 4.1 years
Secondary	Duration of Complete Response (CR)	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.	Up to 3 years
Secondary	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	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.	Baseline up to 3 years
Secondary	Change in HRQoL as Measured by European Quality of Life Five Dimensions Questionnaire-5-level (EQ-5D-5L)	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).	Baseline up to 3 years
Secondary	Change in HRQoL as Measured by EORTC QLQ-Multiple Myeloma Module (MY20)	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.	Baseline up to 3 years
Secondary	Number of Participants with Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability	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.	Up to 4.1 years