Dara-BCD for Rare MGRS

Daratumumab, Bortezomib, Cyclophosphamide, and Dexamethasone Therapy for Patients with Rare Monoclonal Gammopathies of Renal Significance

This is an open-label, multicenter, phase 2 study in subjects with newly diagnosed proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs), OR light chain proximal tubulopathy (LCPT), OR thrombotic Microangiopathy (TMA), OR cryoglobulinemic glomerulonephritis, (CGGN), treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone.

Study Overview

• Status: Not yet recruiting
• Conditions: Monoclonal Gammopathy of Renal Significance (MGRS)
• Intervention / Treatment: Drug: Dara-CyBorD

Detailed Description

The current study aims to investigate daratumumab, bortezomib, cyclophosphamide, and dexamethasone regimen in patients with newly diagnosed PGNMIDs, LCPT, TMA, CGGN. Approximately 10 subjects will receive primary therapy with daratumumab-CyBorD. The primary endpoint is overall complete hematologic response (CHR) rate at 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Liu; Phone Number: 86-13716926210; Email: pkuphliuyang@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of PGNMIDs, OR LCPT, OR TMA, OR CGGN.
2. Evidence of clonal plasma cell in bone marrow.
3. ECOG 0,1,2
4. Neu≥ 1.0*10^9/L, HGB ≥70g/L, PLT ≥ 50*10^9/L.
5. Total bilirubin (TBil) ≤3×upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN;
6. Informed consent explained to, understood by and signed by the patient.

Exclusion Criteria:

1. Prior therapy for MGRS, with the exception of equal or less than 160 mg dexamethasone (or equivalent corticosteroid)
2. Fulfill with the criteria of active multiple myeloma or active lymphoplasmacytic lymphoma.
3. Presence of other tumors which is/are in advanced malignant stage and has/have systemic metastasis;
4. Severe or persistent infection that cannot be effectively controlled;
5. Presence of severe autoimmune diseases or immunodeficiency disease;
6. Patients with active hepatitis B or hepatitis C ([HBVDNA+] or [HCVRNA+]); Patients with HIV infection or syphilis infection;
7. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dara-CyBorD; Daratumumab Cyclophosphamide Bortezomib Dexamethasone	Drug: Dara-CyBorD; Dara-CyBorD will be used for newly diagnosed PGNMID, OR LCPT, OR TMA OR CGGN.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Hematologic Complete Response at the completion of 6 cycles	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Hematologic CR (Complete Response)+ VGPR (very good partial response) at the completion of 6 cyels		6 months
Rate of Hematologic ORR (Overall Response, CR+VGPR+low-dFLC response+PR) at the completion of 6 cyels		6 months
TRAEs	Treatment-related adverse events up to 2 years	2 years
Renal response at 6 months		6 months
MRD status at 6 months		6 months
Renal Survival in 2 years		2 years
Overall Survival in 2 years		2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: daratumumab; TMA; PGNMIDs; LCPT; CGGN
• Additional Relevant MeSH Terms: Immune System Diseases; Hematologic Diseases; Immunoproliferative Disorders; Blood Protein Disorders; Hypergammaglobulinemia; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: 2024PHB134-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No