An international trial with a new standard of care for patients with AL amyloidosis.

Phase 3

Completed

• Conditions: ntreated systemic light chain amyloidosis; Amyloid; Untreated systemic light chain amyloidosis; Cancer - Myeloma

• Registration Number: ACTRN12611000561987
• Lead Sponsor: Australasian Leukaemia and Lymphoma Group (ALLG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-06-01
• Study Completion: 2019-12-06
• Last Update Posted: 3 February 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 110

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 transplant with melphalan 200 mg/m2. Patients who are eligible for transplant with melphalan 200 mg/m2 but decline the procedure, can be enrolled in the study, but are stratified in a separate stratum before randomization.
Eastern Cooperative Oncology Group performance status 0, 1 or 2.
Measurable disease; at least one of the following criteria:
Monoclonal protein more than 10 g/L in serum,
Amyloid-forming (involved) free light chains greater than 75 mg/L with an abnormal kappa-lambda ratio,
Difference between involved and uninvolved free light chains grater than 50 mg/L
Bone marrow with a clonal predominance.
Symptomatic organ involvement (heart, kidney, liver/Gastrointestinal tract, peripheral nervous system).
Hemoglobin of 11 g/dL, absolute neutrophil count of 1500/microL, platelets of 140,000/microL.
Total bilirubin less than 2.5 mg/dL, alkaline phosphatase less than 5 times the upper limit of normal, Alanine transaminase 3 times the upper limit of normal (patients with a documented history of Gilbert’s disease who have a total bilirubin (predominantly unconjugated) greater than 2.5mg/L without any other liver function test abnormalities are still eligible)
Estimated glomerular filtration rate by the modification of diet in renal disease formula greater than 30 ml/min.

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 granulocyte colony stimulating factor only.
Bone marrow plasma cells greater than 30 percent.
Cardiac stage three disease
Chronic atrial fibrillation
Supine systolic blood pressure less than 100mmHg or symptomatic orthostatic hypotension or clinically important autonomic disease
Grade 3 sensory or grade 1 painful peripheral neuropathy.
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 hypersensitivity to bortezomib, boron or mannitol.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To compare in patients treated with melphalan and dexamethasone or bortezomib, melphalan and dexamethasone: the hematologic response after 3 cycles.This will be scored as improved, stable or worsened after 3, 6 and 9 cycles of therapy, then every 6 weeks until disease progression or until 2 years after randomization. After disease progression the patients will be followed for survival and subsequent therapy at least every 3 months for at least 2 years.[The hematologic response after 3 cycles.]