AL amyloidosis
Conditions
Interventions
Treatment consists of bortezomib and dexamethasone followed by stem cell
mobilization, HDM and auto-SCT.
Sponsors
HOVON
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Biopsy proven, systemic, untreated AL amyloidosis requiring systemic chemotherapy, * Age 18 -70 years inclusive at the time of signing the informed consent form, * Measurable plasma cell dyscrasia, defined as a detectable M-protein with serum electrophoresis and/or level of involved FLC> 50 mg/L, * Life expectancy > 3 months, * WHO performance status 0-2, * NYHA stage 1-2, * Negative pregnancy test at inclusion for women of childbearing potential, * Written informed consent.
Exclusion criteria
Exclusion criteria: * Multiple Myeloma stage II and III (Durie and Salmon), * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, * Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule, * Previous treatment for plasma cell dyscrasia * Pregnant or breast feeding females. * Presence of other active malignancy or a history of active malignancy during the past 5 years, with the exception of nonmelanoma skin cancer, stage 0 cervical carcinoma, or treated early-stage prostate cancer provided that prostate-specific antigen is within normal limits, * Hypersensitivity to boron or mannitol, * Uncontrolled infection, * Symptomatic othostatic hypotension defined as a decrease in systolic blood pressure on standing of >20mmHg combined with symptoms like dizziness, cerebral and/or cardial ischemia, *NT pro BNP level > 5000 pg/ml and Troponin T> 0.06 microgram/l (not high senstitivity assay) or NT proBNP level > 5000 pg/ml and Troponin I > 2 times ULN * Symptomatic effusions, defined as pleural effusion or ascites needing drainage therapy, * Positive for HIV or infectious hepatitis, B or C, * Bilirubin > 2x upper limit of normal, * Creatinin clearance grade 2, * NCI CTCAE grade peripheral sensory neuropathy > grade 1 in the presence of neuropathic pain, *NCI CTCAE grade peripheral motor neuropathy > grade 2 * Concurrent diagnosis of B-cel NHL or B-CLL, * Previous organ transplantation. * Unwilling or unable to use adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Hematological CR rate 6 months after auto-SCT. Patients are considered a success if they received HDM and auto-SCT and are in CHR at 6 months, all other patients are considered a failure. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Overall survival measured from the time of registration. Patients still alive or lost to follow up ace censored at the day they were last known to be alive * Progression Free Survival, (hematological), i.e. time from registration until hematological progression, relapse or death, whichever occurs first. * Hematological response rate rate after induction therapy * Response Rate, hematological and organ * Time to response, hematological and organ * Duration of response, hematological and organ * Time to next AL amyloidosis therapy * Safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug * Exploratory assessment of multiparameter flow cytometry quantification of bone marrow plasma cells and change in amyloid deposition in abdominal fat aspiration samples * Evaluation of prognostic factors for survival included in the hematological and organ response criteria | — |
Countries
Netherlands
Outcome results
None listed