A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma
ADVANCE
Phase 2, Open-Label Randomized Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone vs Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
3 other identifiers
interventional
310
1 country
7
Brief Summary
This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone (KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling multiple myeloma than the standard of care treatment, which is lenalidomide, bortezomib, and dexamethasone (VRD).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 multiple-myeloma
Started Feb 2020
Longer than P75 for phase_2 multiple-myeloma
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2020
CompletedStudy Start
First participant enrolled
February 11, 2020
CompletedFirst Posted
Study publicly available on registry
February 13, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2027
March 24, 2026
March 1, 2026
7 years
February 11, 2020
March 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Minimal Residual Disease (MRD) Negativity
MRD will be assessed by the MRD scale ranging from 10 (increased disease detection) to -5 (less to no disease detection) after 8 cycles of therapy.
Up to 32 weeks
Secondary Outcomes (7)
Overall Survival
Up to 16 weeks
Progression Free Survival (PFS)
Up to 16 weeks
Event Free Survival (EFS)
Up to 16 weeks
Rate of Response
Up to 3 years
Rate of MRD Negativity as best response
Up to 3 years
- +2 more secondary outcomes
Study Arms (3)
Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)
EXPERIMENTALParticipants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.
Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)
EXPERIMENTALParticipants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.
Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)
EXPERIMENTALParticipants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.
Interventions
1.3 mg/m2 administered Subcutaneous (SC) or intravenous (IV) on days 1, 4, 8 and 11 of a 21 day treatment cycle for participants randomized to Arm A.
20 mg or 40 mg per dose administered by mouth (PO) or IV. Participants randomized in Arm A: 20 mg/dose on days 1, 4, 8 and 11 on a 21 day treatment cycle; Participants randomized in Arm B: Cycles 1 through 8 - 40mg/dose on days 1, 8 and 15 on a 28-day cycle Participants randomized in Arm C: Cycle 1-2 - 40 mg/dose on days 1, 8, 15 and 22 on a 28-day cycle; Cycles 3-8 - 40mg/dose on Days 1, 8, 15 on a 28-day cycle;
10 or 25 mg/day capsules administered PO. Participants randomized in Arm A: 25 mg/day capsules on Days 1 through 14 of a 21 day cycle.; Participants randomized in Arm B: Cycles 1 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Participants randomized in Arm C: Cycles 1 - 25 mg/day capsules on Days 2 through 21 of a 28 day cycle; Cycles 2 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Maintenance Therapy: 10 mg capsules on Days 1 through 21 on a 28 days cycle.
650 mg administered PO. Participants randomized to Arm C: Cycles 1 through 8 - 650 mg administered on Days 1, 8 and 15.
25 mg administered via IV Participants randomized to Arm C: Cycles 1 through 8 - 25 mg administered on Days 1, 8 and 15.
10 mg administered PO to participants randomized to Arm C prior to the first 4 doses of Daratumumab.
20 mg or 56 mg/m2 per dose administered via IV. Participants randomized to Arm B: Cycle 1 - 20 mg/m2 per dose on Day 1 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle; Participants randomized to Arm C: Cycle 1 - 20 mg/m2 per dose on Day 2 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle
16 mg/kg administered via IV or 1800 mg SC, per treating physician discretion. Participants randomized to Arm C: Cycles 1 though 2 - 16 mg/kg IV or 1800 mg SC on days 1, 8, 15, and 22 of a 28 day cycle; Cycles 3 through 6- 16 mg/kg IV or 1800 mg SC on days 1 and 15 of a 28 day cycle; Cycles 7 through 8 - 16 mg/kg IV or 1800 mg SC on day 1 of a 28 day cycle
Participants who are MRD positive at the conclusion of 8 cycles of study treatment, and were able to have their stem cells that were extracted, will receive ASCT from participants' bone marrow samples.
Eligibility Criteria
You may qualify if:
- Newly diagnosed patients with histologically confirmed Multiple Myeloma (MM) based on the IMWG diagnostic criteria and measurable disease within the past 4 weeks (or past 8 weeks if patient received pre-study MM therapy) based on one of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- Urine monoclonal protein ≥ 200 mg/24 hour
- Involved serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal kappa/lambda ratio.
- Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following (Note: Myeloma defining event does not need to be based on repeat testing done at screening, if previous pathology, radiology, etc., confirm diagnosis of myeloma per IMWG)
- Hypercalcemia: serum calcium \>0.25 mmol/L (\> 1 mg/dL) above upper limit of normal or ≥ 2.75 mmol/L (11 mg/dL)
- Anemia: hemoglobin value \<10 g/dL or \> 2 g/dL below lower limit of normal
- Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or Positron Emission Tomography (PET)-C. For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells
- Clonal bone marrow plasma cell percentage ≥60%
- Involved/un-involved serum free light chain ratio ≥100 and involved free light chain
- ≥100 mg/L.
- \> 1 focal lesion on magnetic resonance imaging study (lesion must be \>5 mm) in size
- For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells
- Creatinine Clearance (CrCl) ≥ 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae
- Age ≥ 18 years at the time of signing the informed consent documentation. Age limit of ≤ 75 years.
- +7 more criteria
You may not qualify if:
- Patients receiving \>1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma:
- Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted
- Bone targeting agents are permitted
- Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted
- Prior treatment with radiotherapy is permitted
- Prior MM treatments, such as Immunomodulating Drugs (IMIDs) or non-MM drugs in clinical trials for smoldering myeloma is permitted with a washout period of 2 weeks from last dose. Smoldering patients previously treated with carfilzomib are excluded.
- Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 2 weeks from last dose (on a trial or outside a trial) are eligible (Note: Measurable disease is defined as one or more of the following: Serum monoclonal protein ≥ 1.0 g/dL, Urine monoclonal protein ≥ 200 mg/24 hour and/ or Involved serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal kappa/lambda ratio)
- Prior or current exposure to any of the following:
- To daratumumab or other anti- Cluster of Differentiation (CD) -38 therapies (unless a re-treatment study)
- Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
- Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
- Patients with plasma cell leukemia
- Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome (POEMS syndrome)
- Patients with amyloidosis
- Patients with known Chronic Obstructive Pulmonary Disorder (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD, and subjects must be excluded if FEV1 \<50% of predicted normal.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Miamilead
- Amgencollaborator
- Janssen Pharmaceuticalscollaborator
Study Sites (7)
University of Miami
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612-9497, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Stony Brook University
Stony Brook, New York, 11794, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institue
Salt Lake City, Utah, 84113, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carl Landgren, MD
University of Miami
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2020
First Posted
February 13, 2020
Study Start
February 11, 2020
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
February 1, 2027
Last Updated
March 24, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share