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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Monoclonal Gammopathy of Renal Significance
• Intervention / Treatment: Drug: Dara-CyBorD

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Lu; Phone Number: 86-13311491805; Email: jin1lu@sina.com
• Study Contact Backup: Name: Yang Liu; Phone Number: 86-13716926210; Email: pkuphliuyang@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Junling Zhuang; Email: zhuangjunling@hotmail.com
      • Principal Investigator: Junling Zhuang, MD
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Yang Liu; Phone Number: +8613716926210; Email: pkuphliuyang@bjmu.edu.cn
      • Principal Investigator: Jin Lu, MD
  • Guangdong
    • Guangzhou, Guangdong, China, 510062
      • Recruiting
      • The first affiliated hospital, Sun Yat-sen University
      • Principal Investigator: Juan Li, MD
      • Contact: Juan Li; Email: 13719209240@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of monoclonal immunoglobulin deposition disease without anti-plasma cell treatment
2. ECOG 0,1,2
3. Neu≥ 1.0*10^9/L, HGB ≥70g/L, PLT ≥ 50*10^9/L.
4. Total bilirubin (TBil) ≤3×upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN;
5. Informed consent explained to, understood by and signed by the patient.

Exclusion Criteria:

1. Prior therapy for MIDD, 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+]);
7. Patients with HIV infection or syphilis infection;
8. 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: N/A
• 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; 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.

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
Renal response at 6 months	Renal response at 6 months	6 months
Cardiac response at 6 months	Cardiac response (for patients with cardiac involvement) at 6 months	6 months
MRD status at 6 months	Minimal residual disease status at 6 months	6 months
Renal Survival in 2 years	Renal Survival in 2 years	2 years
Overall Survival in 2 years	Overall Survival in 2 years	2 years
TRAEs	Treatment-related adverse events up to 2 years	2 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Jin Lu, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 28, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 13, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Daratumumab; Bortezomib; Monoclonal Immunoglobulin Deposition Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Blood Protein Disorders; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Hypergammaglobulinemia; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: 2024PHB134-001

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