Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nutritional and Metabolic Diseases

Neoplasms

Symptoms and General Pathology

Rare Diseases

Monoclonal Gammopathy of Undetermined Significance

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Immunoproliferative Disorders

Hypergammaglobulinemia

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Proteostasis Deficiencies

Metabolic Diseases

Lymphoproliferative Disorders

AL Amyloidosis

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Dexamethasone

Cyclophosphamide

Bortezomib

Daratumumab

Dexamethasone acetate

Immunoglobulins

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Daratumumab:

Cyclophosphamide Bortezomib Dexamethasone

Patient will receive Dara-CyBorD (Daratumumab, Bortezomib, Cyclophosphamide, Dexamethasone) for at least 6 cycles, and then Daratumumab maintainance.

Drug: Daratumumab: 16mg/kg IV dose OR 1800 mg subcutaneously Drug: Cyclophosphamide: 300 mg/m\^2 as an oral or IV dose Drug: Bortezomib: 1.3 mg/m\^2 as an subcutaneous (SC) injection. Drug: Dexamethasone: 20-40mg Patients will receive the above drugs (Dara-CyBorD) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 1 years.

Note: If patients achieve less than hematologic VGPR by cycle 3 or less than PR by cycle 2, treatment plan will be allowed to discontinued, according to treatment principle in systemic light chain amyloidosis.

Dara-CyBorD

Jin Lu

Yang Liu

Junling Zhuang

Junling Zhuang, MD

Jin Lu, MD

Juan Li

Juan Li, MD

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed monoclonal immunoglobulin deposition disease treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone.

The current study aims to investigate daratumumab, bortezomib, cyclophosphamide, and dexamethasone regimen in patients with newly diagnosed monoclonal immunoglobulin deposition disease. Approximately 25 subjects will receive primary therapy with daratumumab-CyBorD. The primary endpoint is overall complete hematologic response (CHR) rate at 6 months.

Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With MIDD

Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With Monoclonal Immunoglobulin Deposition Disease

Hematologic complete response requires absence of monoclonal protein by immunofixation electrophoreses of both serum and urine as well as a normal FLC ratio (FLCr). CR is considered when FLCr was altered in favour of the non-amyloidogenic, uninvolved FLC (uFLC), even though the ratio may not have been normalised.

Cardiac response (for patients with cardiac involvement) at 6 months

Minimal residual disease status at 6 months

Treatment-related adverse events up to 2 years

Peking University People's Hospital

Principal Investigator

Heart and Blood Diseases

Multiple Myeloma

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Hemorrhagic Disorders

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

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.

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

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

Hani Hassoun, MD

Carlyn R Tan, MD

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.

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).

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

A Phase II Study of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone) Plus Daratumumab for Patients With Monoclonal Gammopathy of Renal Significance (MGRS)

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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.

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.

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

Janssen Pharmaceuticals

Memorial Sloan Kettering Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients With MIDD	NCT06418477	Monoclonal Gamm...	Dara-CyBorD	18 Years -	Peking University People's Hospital
A Study of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone) Plus Daratumumab in People With Monoclonal Gammopathy of Renal Significance (MGRS)	NCT06083922	Multiple Myelom... Monoclonal Gamm...	Cyclophosphamid... Bortezomib Dexamethasone Daratumumab	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for monoclonal gammopathy of renal significance