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

NCT ID: NCT06083922

Last Updated: 2025-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-16

Study Completion Date

2026-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma Monoclonal Gammopathy of Renal Significance

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

This trial will include a safety run-in-stage that will enroll patients from either cohort, which purpose is to test the safety of the combination. The run-in-stage will be followed by:

A Simon-two-stage phase II study that will enroll patients with cast nephropathy (cohort A), A pilot study that will enroll patients with all other MGRS excluding AL amyloidosis (cohort B).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A will include patients with cast nephropathy

Planned 8 cycles of CyBorD-Dara SC, treatment will be left to the discretion of the treating physician. It is recommended that patients eligible for ASCT undergo ASCT after 8 cycles of induction and that patient ineligible for ASCT, continue maintenance Bortezomib/Dexamethasone administered every other week with daratumumab SC administered every 4 weeks, for a period of 2 years from start of treatment.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days 1, 8 and 15, Cycles 1-8

Bortezomib

Intervention Type DRUG

Days 1,8,15, Cycles 1-8, Days 1,15 Cycles 9+

Dexamethasone

Intervention Type DRUG

Days 1,2,8, 9,15,16, 22, 23, Cycles 1-8

Daratumumab

Intervention Type DRUG

Days 1,8,15,22, Cycles 1-2, Days 1,15 Cycles 3-6, Day 1 Cycles 7+

Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis

Planned 8 cycles of CyBorD-Dara SC, treatment will be left to the discretion of the treating physician. It is recommended that patients eligible for ASCT undergo ASCT after 8 cycles of induction and that patient ineligible for ASCT, continue maintenance Bortezomib/Dexamethasone administered every other week with daratumumab SC administered every 4 weeks, for a period of 2 years from start of treatment.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days 1, 8 and 15, Cycles 1-8

Bortezomib

Intervention Type DRUG

Days 1,8,15, Cycles 1-8, Days 1,15 Cycles 9+

Dexamethasone

Intervention Type DRUG

Days 1,2,8, 9,15,16, 22, 23, Cycles 1-8

Daratumumab

Intervention Type DRUG

Days 1,8,15,22, Cycles 1-2, Days 1,15 Cycles 3-6, Day 1 Cycles 7+

Interventions

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Cyclophosphamide

Days 1, 8 and 15, Cycles 1-8

Intervention Type DRUG

Bortezomib

Days 1,8,15, Cycles 1-8, Days 1,15 Cycles 9+

Intervention Type DRUG

Dexamethasone

Days 1,2,8, 9,15,16, 22, 23, Cycles 1-8

Intervention Type DRUG

Daratumumab

Days 1,8,15,22, Cycles 1-2, Days 1,15 Cycles 3-6, Day 1 Cycles 7+

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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


* 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


* 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.
* Hepatic Child-Pugh score at worse A (patients are eligible for the phase 2 part but not for the Run-in-Period of the trial).
* Female patients will have to satisfy the following criteria:

* Be postmenopausal for at least 1 year Prior to registration visit, OR
* Be surgically sterile, OR
* If of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
* Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). If patient is female and of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (β-HCG) test \< 14 days prior to registration and consent to ongoing pregnancy testing during the course of the study.
* Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following

* Practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
* Practice true abstinence when this is in line with the preferred and usual lifestyle of he subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception).
* Subjects must have the willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, study procedures, and research procedures.

Exclusion Criteria

* 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.
* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects 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: Subjects 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.
* Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
* Vaccination with live attenuated vaccines within 4 weeks of first study agent administration.
* Plasmapheresis within 28 days before randomization.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hani Hassoun, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Tufts Medical Center (Data Collection Only)

Boston, Massachusetts, United States

Site Status RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, United States

Site Status RECRUITING

Weill Cornell Medical Center (Data Collection Only)

New York, New York, United States

Site Status NOT_YET_RECRUITING

Mount Sinai Hospital (Data Collection Only)

New York, New York, United States

Site Status NOT_YET_RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, United States

Site Status RECRUITING

University of North Carolina (Data Collection Only)

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Hani Hassoun, MD

Role: CONTACT

646-608-3718

Carlyn R Tan, MD

Role: CONTACT

646-608-3778

Facility Contacts

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Raymond L Comenzo, MD

Role: primary

617-636-6454

Hani Hassoun, MD

Role: primary

646-608-3718

Hani Hassoun, MD

Role: primary

646-608-3718

Hani Hassoun, MD

Role: primary

646-608-3718

Hani Hassoun, MD

Role: primary

646-608-3718

Hani Hassoun, MD

Role: primary

646-608-3718

Jorge Monge, MD

Role: primary

Adriana Rossi, MD

Role: primary

212-241-7873

Hani Hassoun, MD

Role: primary

646-608-3718

Carlyn R Tan, MD

Role: backup

646-608-3778

Hani Hassoun, MD

Role: primary

646-608-3718

Samuel Rubinstein, MD

Role: primary

919-966-4431

Related Links

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http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

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22-424

Identifier Type: -

Identifier Source: org_study_id

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