A Study of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone) Plus Daratumumab in People With Monoclonal Gammopathy of Renal Significance (MGRS)

Recruiting now · Phase 2

Conditions studied: Multiple Myeloma, Monoclonal Gammopathy of Renal Significance

In brief

The purpose of this study is to find out whether cyclophosphamide, bortezomib, dexamethasone (CyBorD) with daratumumab SC is a safe treatment combination for MGRS-associated kidney disease including cast nephropathy associated with multiple myeloma. In addition, the researchers will find out whether the study drug combination is an effective treatment for these conditions.

Key facts

Study ID

NCT06083922

Run by

Memorial Sloan Kettering Cancer Center

People needed

20

Starts

2023-10-16

Expected to finish

2026-10-01

Last updated by the study team

2026-07-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Inclusion criteria for cast nephropathy associated with MM:
• Subjects must have a confirmed diagnosis of NDMM as per standard IMWG criteria
• Subjects must have measurable disease, defined as meeting at least 1 of the following criteria ≤ 14 days prior to registration:
• A monoclonal Immunoglobulin (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 0.5 g/dL.
• Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
• Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC ratio is abnormal.
• eGFR must be <40 ml/min/1.73m2
• Subjects must have histologically confirmed diagnosis of monoclonal gammopathy associated CN by kidney biopsy OR If a kidney biopsy is not available, a percentage of urine albumin excretion (%UAE) < 25 % AND FLC > 50 mg/dL
• Inclusion criteria for other MGRS associated renal diseases
• Histologically confirmed diagnosis of MGRS-associated renal disease by kidney biopsy
• Presence of monoclonal gammopathy by serum protein electrophoresis, Immunofixation, or Free Light Chain Assay
• Evidence of plasma cell dyscrasia by bone marrow biopsy confirming clonal plasma cell population
• eGFR <40 ml/min/1.73m2 or 24h urine total protein > 1gm
• Inclusion criteria for both cast nephropathy associated with MM and other MGRS associated renal diseases
• Subjects must be ≥ 18 years of age at time of registration.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 ≤ 14 days prior to registration.
• No evidence of unequivocal recent nephrotoxic exposure (NSAIDs, radiocontrast…)
• No evidence of obstructive nephropathy by ultrasound
• Subjects must have adequate hematology laboratory values within 14 days prior to registration defined by the following:
• Neutrophils ≥ 1.0 × 10\^9 /L (Patients cannot have received G-CSF or GM-CSF within 1 week of screening or pegfilgrastim within 2 weeks of screening to meet eligibility).
• Platelets ≥ 100 × 10\^9 /L for run-in and 75 × 10\^9 /L for phase II (Note: Platelet support is not permitted to help participants meet eligibility criteria).
• hemoglobin ≥ 7.5 g/dL without prior red blood cells [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted.
• Subjects must have adequate hepatic function laboratory values ≤ 14 days prior to registration:
• Aspartate aminotransferase (AST), alkaline phosphatase (AP) or alanine aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN except for patients with a history of elevated total bilirubin, such as in Gilbert's.

You may not qualify if…

• MGRS associated with diseases other than plasma cell dyscrasia (e.g. CLL, B-cell neoplasm, Waldenstrom's macroglobulinemia…)
• Plasma cell leukemia, AL amyloidosis, or POEMS syndrome.
• Treatment with prior drugs aimed at the plasma cell dyscrasia.
• Treatment with prior or concurrent investigational agents aimed at the plasma cell dyscrasia.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery ≤ 14 days before registration.
• Focal radiation therapy within 14 days prior to registration with the exception of palliative- radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
• Disease-related central nervous system involvement.
• The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection.
• Clinically significant cardiac disease, including:
• Myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• Uncontrolled cardiac arrhythmia
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Concurrent malignancy except for treated non-melanoma skin cancer, cervical carcinoma in situ and low-risk prostate CA being monitored without treatment.
• Grade 2 or higher peripheral neuropathy on clinical examination during the screening period.
• Chemotherapy ≤ 14 days of registration.
• Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic halflives, whichever is longer.
• Patients with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal; moderate or severe persistent asthma within the past 2 years. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is <50% of predicted normal
• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• Patients who have a contraindication to the use of any form of anticoagulation or antiplatelet agents.
• The use of strong CYP3A4 and CYP1A2 inducers or inhibitors will not be allowed while patients are treated on this study.
• Patients with Hepatic Child-Pugh score B and C. Note that patients with Hepatic Child-Pugh score A are excluded from the Run-in-Period of the trial
• Patient is:
• Known history of human immunodeficiency virus (HIV) and those who are seropositive for HIV.

Where it is running

• University of North Carolina (Data Collection Only) — Chapel Hill, North Carolina, United States (enrolling)
• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities) — Commack, New York, United States (enrolling)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (enrolling)
• Tufts Medical Center (Data Collection Only) — Boston, Massachusetts, United States
• Weill Cornell Medical Center (Data Collection Only) — New York, New York, United States
• Mount Sinai Hospital (Data Collection Only) — New York, New York, United States

Full record on ClinicalTrials.gov

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