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

NCT06083922 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-424
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Multiple Myeloma; Monoclonal Gammopathy of Renal Significance

Keywords

Cyclophosphamide; Bortezomib; Dexamethasone; Daratumumab; 22-424

Outcome Measures

Primary Outcomes (3)

• Run-in Phase- Dose-limiting toxicity (DLT) rates

  Any participant in the run-in-phase who received at least ≥ 75% of the planned doses of the combination regimen in cycle one will be evaluated for DLTs using NCI-CTCAE.

  2 years

• Phase II (Cohort A) best renal response

  For patients with a decreased eGFR \<50mL/min/1.73 m2 with or without significant proteinuria (UTP\>0.5 gm/24h) at presentation, Assessment of renal response will be based on both the IMWG criteria for patient with decreased eGFR and the amyloid criteria for patients with proteinuria.

  2 years

• Pilot study (Cohort B) best renal response

  For patients with a decreased eGFR \<50mL/min/1.73 m2 with or without significant proteinuria (UTP\>0.5 gm/24h) at presentation, renal response will be assessed using IMWG renal response criteria

  2 years

Study Arms (2)

Arm A will include patients with cast nephropathy

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab

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

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Bortezomib; Drug: Dexamethasone; Drug: Daratumumab

Interventions

Cyclophosphamide DRUG

Days 1, 8 and 15, Cycles 1-8

Arm A will include patients with cast nephropathy; Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis

Bortezomib DRUG

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

Arm A will include patients with cast nephropathy; Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis

Dexamethasone DRUG

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

Arm A will include patients with cast nephropathy; Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis

Daratumumab DRUG

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

Arm A will include patients with cast nephropathy; Arm B will include all other MGRS associated diseases with the exclusion of AL amyloidosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (11)

Tufts Medical Center (Data Collection Only)

Boston, Massachusetts, 02111, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

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

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Weill Cornell Medical Center (Data Collection Only)

New York, New York, 10021, United States

NOT YET RECRUITING

Mount Sinai Hospital (Data Collection Only)

New York, New York, 10029, United States

COMPLETED

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

University of North Carolina (Data Collection Only)

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; Bortezomib; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Hani Hassoun, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hani Hassoun, MD

CONTACT

646-608-3718; hassounh@mskcc.org

Carlyn R Tan, MD

CONTACT

646-608-3778

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: October 16, 2023
• Study Start: October 16, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (11)