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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 : May 30, 2019
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 flow (NGF) or next generation sequencing (NGS) following high-dose therapy (HDT) and autologous stem cell transplant (ASCT), with or without consolidation therapy.

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 : May 30, 2021
Estimated Study Completion Date : May 13, 2023

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: Approximately 3 years ]
    PFS is defined as duration from date of randomization to either PD or 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]) and/or in 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); and/or only in participants without measurable serum and urine M-protein levels and without measurable involved FLC levels, Bone Marrow PC%: absolute increase >=10%; and/or appearance of new lesion(s), >=50% increase from nadir in sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of >1 lesion, or >=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >=50% increase in circulating PCs if this is the only measure of disease.

  2. Percentage of Participants with Overall Minimal Residual Disease (MRD) Negative Status [ Time Frame: Up to 36 months ]
    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 36 months ]
    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 36 months ]
    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: Approximately 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: Approximately 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.

  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 36 months ]
    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 36 months ]
    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 36 months ]
    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 Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Approximately 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Have newly diagnosed multiple myeloma with a history of 4 to 8 total cycles of induction with or without consolidation therapy and have received high-dose therapy (HDT) and autologous stem cell transplantation (ASCT): (a) for participants who have not received consolidation therapy, the participant must be 60 to 100 days post-transplant at the time of randomization; and (b) for participants treated with consolidation therapy, the participant must be within 60 days of the last dose of consolidation therapy at the time 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
  • Have archived bone marrow biopsy samples collected before induction treatment (that is, at diagnosis) or before transplant (for example, at the end of induction). Archived bone marrow samples will be used for calibration of myeloma clonal cells to facilitate assessment of primary end point by next generation sequencing (NGS). 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 tissue for minimal residual disease (MRD) assessment: (i) 5 slides, 5 micrometer each, of non-decalcified bone marrow, or (ii) 5 slides, 5 micrometer each, bone marrow aspirate smear
  • Must have residual disease as defined by detectable MRD by next generation flow (NGF) assay
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

Exclusion Criteria:

  • Have peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
  • Have any prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, and concurrence by the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
  • Have had prior treatment/therapy with: (a) Anti-cluster of differentiation 38 (CD38) antibody at any time, (b) Radiation within 14 days of randomization, 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) Seropositive 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

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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     History of Changes
Other Study ID Numbers: CR108599
54767414MMY3021 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
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
Antibodies, Monoclonal
Daratumumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents