The primary study design was a phase III study with randomization with the hypothesis that bortezomib+dexamethasone has a better outcome than only dexamthe. However due to slow inclusion the expectation was that the primary endpoint could not be…
ID
Bron
Verkorte titel
Aandoening
de novo amyloid (AL) amyloidosis
Ondersteuning
(HOVON), HOVON Data Center
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
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.
Achtergrond van het onderzoek
Study phase: Phase III.
Study objective:
Primary:
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.
Secondary:
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.
Study design:
International multi-center, open label, prospective 1 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.
Doel van het onderzoek
The primary study design was a phase III study with randomization with the hypothesis that bortezomib+dexamethasone has a better outcome than only dexamthe. However due to slow inclusion the expectation was that the primary endpoint could not be reached with already 23 patients included. Of those 23 patients, 16 patients where randomized to bortezomib induction. No safety issues were identified. Because the scientific value of the study was still present and medical important information was collected it was
considered unethical to stop the study. Therefore it was decided to close the control arm of the study and continue as a 1 arm study.
Onderzoeksopzet
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.
Onderzoeksproduct en/of interventie
Treatment arm consists of bortezomib and dexamethasone followed by stem cell mobilization, HDM and auto-SCT.
Publiek
Department of Hematology/B02.226
P.O. Box 85500
M.C. Minnema
Utrecht 3508 GA
The Netherlands
+31 30 2507230
m.c.minnema@umcutrecht.nl
Wetenschappelijk
Department of Hematology/B02.226
P.O. Box 85500
M.C. Minnema
Utrecht 3508 GA
The Netherlands
+31 30 2507230
m.c.minnema@umcutrecht.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
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.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
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.
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL3072 |
| NTR-old | NTR3220 |
| Ander register | EudraCT : 2010-021445-42 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |