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

Monoclonal Gammopathy of Renal Significance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06418477
• Other study ID #: 2024PHB134-001
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Peking University People's Hospital
• Contact: Jin Lu
• Phone: 86-13311491805
• Email: jin1lu[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Immunoglobulin Light-chain Amyloidosis
• Monoclonal Gammopathy of Renal Significance
• Monoclonal Gammopathy of Undetermined Significance
• Paraproteinemias

Intervention

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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of Hematologic CR (Complete Response)+ VGPR (very good partial response) at the completion of 6 cyels		6 months
Secondary	Rate of Hematologic ORR (Overall Response, CR+VGPR+low-dFLC response+PR) at the completion of 6 cyels		6 months
Secondary	Renal response at 6 months	Renal response at 6 months	6 months
Secondary	Cardiac response at 6 months	Cardiac response (for patients with cardiac involvement) at 6 months	6 months
Secondary	MRD status at 6 months	Minimal residual disease status at 6 months	6 months
Secondary	Renal Survival in 2 years	Renal Survival in 2 years	2 years
Secondary	Overall Survival in 2 years	Overall Survival in 2 years	2 years
Secondary	TRAEs	Treatment-related adverse events up to 2 years	2 years