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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: EUCTR
Last refreshed on: 26 February 2018
Main ID:  EUCTR2010-022395-31-DE
Date of registration: 18/10/2012
Prospective Registration: Yes
Primary sponsor: European Myeloma Network
Public title: Clinical trial of Melphalan and Dexamethasone versus Bortezomib, Melphalan and Dexamethasone for untreated patients with systemic light-chain (AL) amyloidosis
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 - AC-004-EU
Date of first enrolment: 25/10/2012
Target sample size: 110
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022395-31
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: Combination of IMPs
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Czech Republic Denmark France Germany Greece Italy Netherlands Spain
Sweden United Kingdom
Contacts
Name: Amyloidose-Zentrum   
Address:  Im Neuenheimer Feld 410 69120 Heidelberg Germany
Telephone: +496221568009
Email: stefan.schoenland@med.uni-heidelberg.de
Affiliation:  Universitätsklinikum Heidelberg
Name: Amyloidose-Zentrum   
Address:  Im Neuenheimer Feld 410 69120 Heidelberg Germany
Telephone: +496221568009
Email: stefan.schoenland@med.uni-heidelberg.de
Affiliation:  Universitätsklinikum Heidelberg
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 kappa and 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; at least one of the following criteria:
a) monoclonal protein >10 g/L in serum,
b) amyloid-forming (involved) FLC >75 mg/L with an abnormal Kappa/lampda- ratio,
c) difference between involved and uninvolved FLC >50 mg/L,
d) bone marrow with a clonal predominance.
- Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
- Hemoglobin =11 g/dL, absolute neutrophil count =1500/microL, platelets =140,000/microL.
-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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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.
- 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 51mL/min, left ventricular ejection fraction >45%, and bilirubin - 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:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
AL amyloidosis
MedDRA version: 14.1 Level: PT Classification code 10002022 Term: Amyloidosis System Organ Class: 10021428 - Immune system disorders
Therapeutic area: Diseases [C] - Cancer [C04]
Intervention(s)

Trade Name: Velcade
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Trade Name: Fortecortin
Product Name: Dexamethason
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Other descriptive name: DEXAMETHASONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Alkeran
Product Name: Melphalan
Pharmaceutical Form: Coated tablet
INN or Proposed INN: MELPHALAN
CAS Number: 148-82-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)
Main Objective: To compare hematologic response after 3 cycles in patients treated with MDex or BMDex
Primary end point(s): Hematologic response
Secondary Objective: To compare in patients treated with MDex or BMDex:
- complete hematologic response rate after 3 cycles and after completion of therapy;
- hematologic response rate at completion of therapy;
- organ response rates at 3, 6, 9 and 12 months;
- treatment-related mortality;
- toxicity;
- overall and progression-free survival;
- time to hematologic and organ response;
- quality of life.
Timepoint(s) of evaluation of this end point: Hematologic response after 3 cycles of therapy
Secondary Outcome(s)
Secondary end point(s): 1. complete hematologic response rate
2. hematologic response rate
3. organ response rates
4. treatment related mortality
5. toxicity
6. overall and progression-free survival
7. time to hematologic and organ response
8. quality of life
Timepoint(s) of evaluation of this end point: 1. after 3 cycles and after completion of therapy
2. at completion of therapy
3. at 3, 6, 9, 12 months

8. before each cycle, at End of treatment visit, Every 6 weeks before progression, Every 3 months after progression
Secondary ID(s)
2010-022395-31-IT
AC-004-EU
Source(s) of Monetary Support
European Myeloma Network
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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