search  
 


Home

Who are we?

Why
register?


Signup for
registration


Online registration

Log in to register
your trial


Search a trial

NRT en CCMO

Contact

NEDERLANDS





MetaRegister
van CCT (UK)


ISRCTN-Register
van CCT (UK)


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.


- candidate number10822
- NTR NumberNTR3220
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR2-jan-2012
- Secondary IDs2010-021445-42 EudraCT
- Public TitleA 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 TitleA 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.
- ACRONYMHOVON 104 AL Amyloidosis
- hypothesisThe 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) studiedDe novo amyloid (AL) amyloidosis
- Inclusion criteria1. 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 criteria1. 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 receivedyes
- multicenter trialyes
- randomisedyes
- masking/blindingNone
- controlActive
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 3-jan-2012
- planned closingdate3-jan-2018
- Target number of participants114
- InterventionsTreatment 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 outcomeHematological 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 outcome1. 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.
- Timepoints1. 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 sitewww.hovon.nl
- statusplanned
- CONTACT FOR PUBLIC QUERIESMD, PhD M.C. Minnema
- CONTACT for SCIENTIFIC QUERIESMD, PhD M.C. Minnema
- Sponsor/Initiator Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
- Funding
(Source(s) of Monetary or Material Support)
Dutch Cancer Society, Janssen Pharma N.V.
- PublicationsN/A
- Brief summaryStudy 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, 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)
- RECORD2-jan-2012 - 16-jan-2012


  • Indien u gegevens wilt toevoegen of veranderen, kunt u een mail sturen naar nederlands@trialregister.nl