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.

Phase 1

Conditions: AL Amyloidosis
MedDRA version: 16.1Level: HLGTClassification code 10035227Term: Plasma cell neoplasmsSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2010-022395-31-CZ

Lead Sponsor: E.M.N. - EUROPEAN MYELOMA NETWORK

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 110

Inclusion Criteria

1. Histologic diagnosis of amyloidosis.
2. Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis or immunohistochemistry of amyloid deposits must provide clear evidence of K or ? light chains in those who present with peripheral neuropathy or heart as the dominant organ involvement. 3. 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.
4. Patients must be = 18 years of age.
5. ECOG performance status 0,1 or 2.
6. 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/? ratio
• difference between involved and uninvolved FLC >50 mg/L
• bone marrow with a clonal predominance
7. Symptomatic organ involvement
8. Hemoglobin =11 g/dL, absolute neutrophil count =1500/mcL, platelets =140,000/mcL.
9. Total bilirubin <2.5 mg/dL, alkaline phosphatase <5 × u.l.n., ALT <3 × u.l.n..
10. Estimated glomerular filtration rate (eGFR) by the MDRD formula >30
ml/min.
11. 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.
12. Women must be either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control
13. 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Amyloid-specific syndrome
2. Isolated soft tissue involvement.
3. Presence of non-AL amyloidosis.
4. Previous treatment for plasma cell disease.
5. Bone marrow plasma cells >30%.
6. 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.
7. Repetitive ventricular arrhythmias on 24h Holter ECG in spite of anti-arrhythmic treatment or chronic atrial fibrillation
8. Supine systolic blood pressure <100 mmHg or symptomatic orthostatic hypotension or clinically important autonomic disease
9. Grade 3 sensory or grade 1 painful peripheral neuropathy.
10. 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.
11. Pregnant or nursing women.
12. Clinically overt multiple myeloma with lytic bone lesions
13. 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.
14. 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.
15. HIV positive.
16. Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
17. Patients with hypersensitivity to bortezomib, boron or mannitol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the hematologic response after 3 cycles of therapy.;Secondary Objective: 1. Complete hematologic response rate after 3 cycles and after<br>completion of therapy; <br>2. Hematologic response rate at completion of<br>therapy; <br>3. Organ response rates at 3, 6, 9 and 12 months; <br>4. Treatmentrelated<br>mortality; <br>5. Toxicity; <br>6. Overall and progression-free survival; <br>7. Time to hematologic and organ response; <br>8. Quality of life.;Primary end point(s): Hematologic response after 3 cycles of therapy.

Secondary Outcome Measures

Name	Time	Method

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