|- candidate number||10822|
|- NTR Number||NTR3220|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||2-jan-2012|
|- Secondary IDs||2010-021445-42 EudraCT|
|- Public Title||A multicenter, randomized phase III study of bortezomib and dexamethasone compared with dexamethasone alone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.|
|- Scientific Title||A multicenter, randomized phase III study of bortezomib and dexamethasone compared with dexamethasone alone as induction treatment followed by high dose melphalan (HDM) and autologous stem cell transplantation (SCT) in patients with de novo amyloid light chain (AL) amyloidosis.|
|- ACRONYM||HOVON 104 AL Amyloidosis|
|- hypothesis||The hypothesis to be testes is that the outcome in the bortezomib plus dexamethasone is better compared to dexamethasone alone, both followed by HDM and auto-SCT.|
|- Healt Condition(s) or Problem(s) studied||De novo amyloid (AL) amyloidosis|
|- 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||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 < 30 ml/min (after rehydration);
14. Absolute neutrophil count < 1.0 × 109/L;
15. NCI CTCAE grade peripheral sensory neuropathy > 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.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||3-jan-2012|
|- planned closingdate||3-jan-2018|
|- Target number of participants||114|
|- Interventions||Treatment arm A consists of dexamethasone induction chemotherapy followed by stem cell mobilization, HDM and auto-SCT.|
Treatment arm B consists of bortezomib and dexamethasone followed by stem cell mobilization, HDM and auto-SCT.
|- Primary outcome||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 outcome||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.
|- Timepoints||1. At entry: Within 3 weeks before start of treatment;|
2. After each induction cycle;
3. After stem cell mobilisation and before HDM;
4. At 3 months after date of auto-SCT;
5. At 6 months after date of auto-SCT;
6. During follow up every 3 months, calculated from the date of auto-SCT (or date off protocol treatment);
7. Suspected CHR: If serum and urine IF becomes negative and FLC ratio normal with normal involved FLC a bone marrow examination has to be performed to establish CHR.
|- Trial web site||www.hovon.nl|
|- CONTACT FOR PUBLIC QUERIES||MD, PhD M.C. Minnema|
|- CONTACT for SCIENTIFIC QUERIES||MD, PhD M.C. Minnema|
|- Sponsor/Initiator ||Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)|
(Source(s) of Monetary or Material Support)
|Dutch Cancer Society, Janssen Pharma N.V.|
|- Brief summary||Study phase: Phase III.
To determine the efficacy of bortezomib plus dexamethasone compared to dexamethasone followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive.
To asses the safety of bortezomib plus dexamethasone in the induction regimen followed by HDM and autologous SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive.
International multi-center, randomized, open label, 2 arm.
Duration of treatment:
Expected duration of induction and intensification is in total 4-5 months. All patients will be followed until 5 years after registration.
|- Main changes (audit trail)|
|- RECORD||2-jan-2012 - 16-jan-2012|