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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 December 2017
Main ID:  NCT01277016
Date of registration: 10/01/2011
Prospective Registration: Yes
Primary sponsor: European Myeloma Network
Public title: A Trial for Systemic Light-chain (AL) Amyloidosis EMN-03
Scientific title: A Randomized Open-label Multicenter Phase III Trial of Melphalan and Dexamethasone (MDex) Versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients With Systemic Light-chain (AL) Amyloidosis
Date of first enrolment: January 2011
Target sample size: 110
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT01277016
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 3
Countries of recruitment
Italy
Contacts
Name:     Giovanni mr Palladini, Proff
Address: 
Telephone:
Email:
Affiliation:  Amyloidosis Research and Treatment Center, Pavia, Italy
Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologic diagnosis of amyloidosis.

- Genetic testing must be negative for transthyretin mutations associated with
hereditary amyloidosis or immunohistochemistry of amyloid deposits must provide clear
evidence of kappa or lambda light chains in those who present with peripheral
neuropathy or heart as the dominant organ involvement.

- Not eligible for ASCT with melphalan 200 mg/m2. Patients who are eligible for SCT with
melphalan 200 mg/m2 but decline the procedure, can be enrolled in the study, but are
stratified in a separate stratum before randomization.

- Patients must be 18 years of age.

- ECOG performance status 0,1 or 2.

- Measurable disease; al least one of the following criteria:

- monoclonal protein >10 g/L in serum,

- amyloid-forming (involved) FLC >75 mg/L with an abnormal K/L ratio,

- difference between involved and uninvolved FLC >50 mg/L,

- bone marrow with a clonal predominance.

- Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous
system). Definition of organ involvement is defined.

- Hemoglobin =11 g/dL, absolute neutrophil count =1500/mikroL, platelets
=140,000/mikroL.

- Total bilirubin <2.5 mg/dL, alkaline phosphatase <5 × u.l.n., ALT <3 × u.l.n..

- Estimated glomerular filtration rate (eGFR) by the MDRD formula >30 ml/min.

- Only patients who are informed of the investigational nature of this study and sign
and give written informed consent in accordance with institutional, national and
European guidelines are eligible to participate.

- Women must be either post-menopausal or surgically sterilized or willing to use an
acceptable method of birth control (i.e. a hormonal contraceptive, diaphragm with
spermicide, condom with spermicide, or abstinence) for the duration of the study. All
females of childbearing potential must have a blood test or urine study within 2 weeks
prior to registration to rule out pregnancy.

- Men must agree to use an acceptable method for contraception for the duration of the
study.

Exclusion Criteria:

- Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only
evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy
specimen or in a plasmacytoma is not indicative of systemic amyloidosis.

- Isolated soft tissue involvement.

- Presence of non-AL amyloidosis.

- Previous treatment for plasma cell disease. A single previous cycle of dexamethasone
or steroid equivalent (maximum cumulative dexamethasone dose 160 mg) is allowed; in
this case baseline data must be obtained after steroid administration. Previous stem
cell harvest is allowed, provided that mobilization is performed with G-CSF only.

- Bone marrow plasma cells >30%.

- Cardiac stage III disease: both cTnT > 0.035 ng/mL (or in place of cTnT the cTnI >
0.10 ng/mL) AND simultaneous NT-proBNP >332 ng/L. These subject can be enrolled in the
ancillary phase II study.

- Repetitive ventricular arrhythmias on 24h Holter ECG in spite of anti-arrhythmic
treatment.

- Chronic atrial fibrillation

- Supine systolic blood pressure <100 mmHg or symptomatic orthostatic hypotension or
clinically important autonomic disease

- Grade 3 sensory or grade 1 painful peripheral neuropathy.

- Patients with AL who are eligible for ASCT with 200 mg/m2 of melphalan. These are
patients <65 years of age, without cardiac involvement (determined according to the
consensus criteria), with eGFR >51mL/min, left ventricular ejection fraction >45%, and
bilirubin <2.0 mg/dL. Patients who are eligible for SCT with melphalan 200 mg/m2 but
decline the procedure, can be enrolled in the study, but are stratified in a separate
stratum before randomization.

- Pregnant or nursing women.

- Clinically overt multiple myeloma with lytic bone lesions

- Patients with uncontrolled infection or active malignancy with the exception of
adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
adequately treated Stage I cancer from which the patient is currently in complete
remission, or any other cancer from which the patient has been disease-free for 5
years.

- Patients with medically documented cardiac syncope, uncompensated NYHA Class 3 or 4
congestive heart failure, or myocardial infarction within the previous 6 months are
not eligible.

- HIV positive.

- Patients with serious medical or psychiatric illness likely to interfere with
participation in this clinical study.

- Patients with hypersensitivity to bortezomib, boron or mannitol.



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
AL Amyloidosis
Intervention(s)
Drug: BMDex
Primary Outcome(s)
Number of Patients in CR and PR measured by level of serum light chain monoclonal protein [Time Frame: 3 cycles of therapy]
Secondary Outcome(s)
Compare haematology response [Time Frame: 2 years]
Secondary ID(s)
2010-022395-31
EMN-03
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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