Systemic AL Amyloidosis
Conditions
Keywords
rapid dFLC response, daratumumab, systemic al amyloidosis
Brief summary
Light chain amyloidosis (AL amyloidosis) is a rare plasma cell dyscrasia characterized by the deposition of insoluble amyloid fibrils in multiple organ systems. The treatment of amyloidosis primarily relies on anti-plasma cell therapy and supportive care. The application of anti-plasma cell therapy has significantly improved outcomes in patients with AL amyloidosis. Standard first-line therapy typically includes daratumumab, bortezomib, cyclophosphamide, and dexamethasone (Dara-BCD), achieving a complete hematologic response in nearly 60% of patients.The depth and speed of the hematologic response are strongly correlated with organ response and overall survival. An early achievement of a complete hematologic response is particularly crucial in cases of AL amyloidosis characterized by significant organ involvement. The median time to a hematologic response for the daratumumab based treatment is only 7-9 days. The retrospective data showed that the hematologic response in Day 7 in Cycle 1 (C1D7) may predict the complete hematologic response rate. In order to validate the conclusion, the investigator design this prospective study.
Interventions
Bortezomib is administered subcutaneously. The dosage range from 0.7 to 1.3 mg/m2 on days 1, 8, 15, and 22 of each cycle, for a maximum of 6 cycles
DRUGDara IV
The treament follow the clinical routine practice, as daratumumab 16mg/kg iv qw OR dara SC 1800mg initially. The treatment schedule involve weekly administrations during cycles 1 to 2, following by biweekly administrations during cycles 3 to 6. Subsequently, monthly administrations are given as monotherapy.
DRUGDexamethasone
Dexamethasone is administered intravenously at a dose of 40 mg weekly for each cycle, for a maximum of 6 cycles. For patients over 70 years of age or with severe edema, heart failure, or uncontrolled diabetes mellitus, dexamethasone can be administered at a dose of 10-20 mg per week.
Some patients may receive cyclophosphamide orally or intravenously at a dosage of 300 mg/m2 weekly.
DRUGDara SC
The treament follow the clinical routine practice, as daratumumab 16mg/kg iv qw OR dara SC 1800mg initially. The treatment schedule involve weekly administrations during cycles 1 to 2, following by biweekly administrations during cycles 3 to 6. Subsequently, monthly administrations are given as monotherapy.
Sponsors
Peking University People's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of systemic AL amyloidosis; 2. Daratumumab, bortezomib, dexamethasone used in treatment; 3. Informed consent explained to, understood by and signed by the patient; 4. dFLC ≥ 50 mg/L;
Exclusion criteria
1. Fulfill with the criteria of active multiple myeloma or active lymphoplasmacytic lymphoma; 2. Presence of other tumors which is/are in advanced malignant stage and has/have systemic metastasis; 3. Severe or persistent infection that cannot be effectively controlled; 4. Presence of severe autoimmune diseases or immunodeficiency disease; 5. Patients with active hepatitis B or hepatitis C (\[HBVDNA+\] or \[HCVRNA+\]); Patients with HIV infection or syphilis infection; 6. 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 |
|---|---|
| Complete hematologic response | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall hematologic response | 6 months | — |
| At least one organ response | 12 months | — |
| Minimal residual disease | 6 months, 12 months | Bone marrow miminal residual disease |
| TTNT | 12 months | Time to next treatment |
| MOD-EFS | 12 months | Major Organ Deterioration Event-Free Survival (MOD-EFS) is defined as the time from the beginning of treatment to hematologic progression, clinical manifestation of end-stage cardiac or renal disease, initiation of subsequent other anti-plasma cell therapy, or death, whichever occur first |
| MOD-PFS | 12 months | Major organ deterioration progression-free survival (MOD-PFS) is defined as the time from the beginning of treatment to death, clinical manifestation of end-stage cardiac or renal failure, or hematologic progression, whichever occur first |
Countries
China
Contacts
CONTACTYang Liu, M.D.
Outcome results
None listed