de novo amyloid (AL) amyloidosis
Conditions
Interventions
Treatment arm consists of bortezomib and dexamethasone followed by stem cell mobilization, HDM and auto-SCT.
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland
(HOVON), HOVON Data Center
Eligibility
Inclusion criteria
Inclusion criteria: 1. Biopsy proven, systemic, untreated AL amyloidosis requiring systemic chemotherapy; 2. Age 18 -70 years inclusive at the time of signing the informed consent form; 3. Measurable plasma cell dyscrasia, defined as a detectable M-protein with serum electrophoresis and/or level of involved FLC > 50 mg/L; 4. Life expectancy > 3 months; 5. WHO performance status 0-2; 6. NYHA stage 1-2; 7. Negative pregnancy test at inclusion for women of childbearing potential; 8. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Multiple Myeloma stage II and III (Durie and Salmon); 2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form; 3. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule; 4. Previous treatment for plasma cell dyscrasia; 5. Pregnant or breast feeding females; 6. 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; 7. Hypersensitivity to boron or mannitol; 8. Uncontrolled infection; 9. Symptomatic orthostatic hypotension defined as a decrease in systolic blood pressure on standing of >20 mmHg combined with symptoms like dizziness, cerebral and/or cardial ischemia; 10. Symptomatic effusions, defined as pleural effusion or ascites needing drainage therapy; 11. Positive for HIV or infectious hepatitis, B or C (screening obligatory); 12. Bilirubin > 2x upper limit of normal; 13. Creatinine clearance grade 2; 16. NCI CTCAE grade peripheral sensory neuropathy > grade 1 in the presence of neuropathic pain; 17. NCI CTCAE grade peripheral motor neuropathy > grade 2; 18. Concurrent diagnosis of B-cell NHL or B-CLL; 19. Previous organ transplantation; 20. 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 after auto-SCT; all other patients are considered a failure. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival measured from the time of registration. Patients still alive or lost to follow up are censored at the day they were last known to be alive; 2. Progression Free Survival, (hematological), i.e. time from registration until hematological progression, relapse or death, whichever occurs first; 3. Hematological response rate rate after induction therapy; 4. Response rate, hematological and organ; 5. Time to response, hematological and organ; 6. Duration of response, hematological and organ; 7. Time to next AL amyloidosis therapy; 8. Safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug; 9. Exploratory assessment of multiparameter flow cytometry quantification of bone marrow plasma cells and change in amyloid deposition in abdominal fat aspiration samples; 10. Evaluation of prognostic factors for survival included in the hematological and organ response criteria. | — |
Contacts
Public ContactM.C. Minnema
University Medical Center Utrecht Department of Hematology/B02.226 P.O. Box 85500
Outcome results
None listed