AL Amyloidosis, Amyloidosis; Systemic
Conditions
Keywords
t(11;14), Rapid Response, AL amyloidosis
Brief summary
Achievement of complete hematologic response (CHR) is vital for systemic AL amyloidosis. Currently, the CHR rate of daratumumab, bortezomib, and dexamethasone (DBD) is close to 60%. Considering that Bcl-2 inhibitor is effective for AL amyloidosis with t(11; 14) and the median hematologic onset time of DBD is 7 days. We design a a prospective study on AL amyloidosis with t(11; 14). All patients receive DBD at the beginning. Patient will receive DBD for at least 6 cycles if achieve rapid hematologic response at day 7, while other patients will receive daratumumab, venetoclax and dexamethasone.
Detailed description
The goal of this clinical trial is to optimize the first line treatment for systemic AL amyloidosis with t(11;14). The aim of this study is to pursue early complete hematologic response. The primary endpoint is overall complete hematologic response (CHR) rate at 6 months. Participants will be treated according to the hematologic response after 7 days. If the patient get rapid response after 7 days, he/she will receive daratumumab, venetoclax and dexamethasone (DBD) for at least 6 cycles. If the patient do not get rapid response, he/she will receive daratumumab, venetoclax and dexamethasone.
Interventions
DRUGDaratumumab
Daratumumab 16 mg/kg was administered intravenously weekly in cycles one and two, every two weeks for cycles three to six, for at least 6 cycles. Daratumumab and hyaluronidase-fihj 1800mg is allowed according to the patients' choice.
DRUGBortezomib
All patients received 1.0-1.3 mg/m2 subcutaneous bortezomib once weekly of 28 days each for at 6 cycles.
DRUGDexamethasone
All patients received 20-40 mg oral or intravenous dexamethasone
DRUGVenetoclax
All patients received venetoclax 400mg daily.
Sponsors
Jin Lu, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of systemic AL amyloidosis; 2. Daratumumab, bortezomib, dexamethasone used in 1st line treatment; 3. Life expectancy greater than 12 weeks; 4. HGB ≥70g/L; 5. Blood oxygen saturation \>90%; 6. Total bilirubin (TBil) ≤3×upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN; 7. Informed consent explained to, understood by and signed by the patient.
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 \[HCVRNA+\]); 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall CHR rate at 6 months | Overall CHR rate at 6 months | Overall complete hematologic response rate at 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac response at 6 months | Cardiac response at 6 months | Cardiac response at 6 months |
| Renal response at 6 months | Renal response at 6 months | Renal response at 6 months |
| Hepatic response at 6 months | Hepatic response at 6 months | Hepatic response at 6 months |
| Estimated 2-year PFS | Estimated 2-year PFS | Estimated 2-year progression free survival |
| Estimated 2-year OS | Estimated 2-year overall survival | Estimated 2-year overall survival |
| MRD status at 6 months | MRD status at 6 months | Minimal residual disease status at 6 months |
| TRAEs | TRAEs | treatment-related adverse events up to 6 months |
Countries
China
Contacts
CONTACTJin Lu
PRINCIPAL_INVESTIGATORJin Lu
Peking University People's Hospital
Outcome results
None listed