Monoclonal Gammopathy of Renal Significance
Conditions
Keywords
Daratumumab, Bortezomib, Monoclonal Immunoglobulin Deposition Disease
Brief 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.
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.
Interventions
DRUGDara-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.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Hematologic Complete Response at the completion of 6 cycles | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 months | Renal response at 6 months |
| Cardiac response at 6 months | 6 months | Cardiac response (for patients with cardiac involvement) at 6 months |
| Rate of Hematologic CR (Complete Response)+ VGPR (very good partial response) at the completion of 6 cyels | 6 months | — |
| Renal Survival in 2 years | 2 years | Renal Survival in 2 years |
| Overall Survival in 2 years | 2 years | Overall Survival in 2 years |
| TRAEs | 2 years | Treatment-related adverse events up to 2 years |
| MRD status at 6 months | 6 months | Minimal residual disease status at 6 months |
Countries
China
Contacts
Primary ContactJin Lu
Backup ContactYang Liu
Outcome results
None listed