Back to resultsCyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis
Primary Purpose
Amyloidosis
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
cyclophosphamide
lenalidomide
dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Amyloidosis focused on measuring amyloidosis, lenalidomide, cyclophosphamide, dexamethasone
Eligibility Criteria
Inclusion criteria:
- Diagnosis of AL amyloidosis.
- Evidence of a monoclonal light chain at serum and/or urine immunofixation electrophoresis.
- Elevated circulating free light chain (of the type identified by immunofixation) above the upper limit of the normal range and abnormal kappa/lambda ratio.
- Previously treated and requiring further treatment.
- Symptomatic organ involvement.
- Bone marrow plasma cell <30%.
- Echocardiographic ejection fraction >40%.
- Troponin I <0.1 ng/mL.
- Hemoglobin >10 g/dL.
- Absolute neutrophil count >1500/uL.
- Platelet count >140000/uL.
- Total bilirubin <2.5 mg/dL.
- Alkaline phosphatase <4 x upper reference limit (u.r.l.).
- ALT <3 x u.r.l..
- Glomerular filtration rate >30 mL/min.
- Performance status ECOG 1-3.
- Female subjects of childbearing potential must have two negative pregnancy tests prior to starting study drug.
Exclusion Criteria:
- Prior treatment with the association of cyclophosphamide, lenalidomide and dexamethasone or with lenalidomide.
- Requirement for other concomitant chemotherapy, immunotherapy or radiotherapy, or any investigational ancillary therapy.
- Presence of other active malignancies, with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limits.
- Clinically overt multiple myeloma.
- Uncontrolled infection.
- New York Heart Association (NYHA) class 4 heart failure.
- Enzyme documented myocardial infarction within 6 months before enrollment.
- Grade 2 or 3 atrioventricular block (Mobitz type I is permitted).
- Repetitive ventricular arrhythmias at 24 h Holter electrocardiogram in spite of treatment with amiodarone.
- Supine systolic blood pressure <90 mmHg, or symptomatic orthostatic hypotension, or a decrease in systolic blood pressure on standing of >20 mmHg in spite of being treated for orthostatic hypotension.
- Prior history of thrombosis or venous thromboembolism or pulmonary embolism. Prior diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency.
- Indication to receive clopidogrel, ticlopidine or warfarin.
- Factor X level <20%.
- Poorly controlled diabetes mellitus (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months).
- Previous or ongoing psychiatric illness (with the exclusion of reactive depression).
- Pregnant or nursing women.
Sites / Locations
- Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
The participants receive up to 9 28-day cycles of cyclophosphamide: 500 mg orally on days 1, 8, 15; lenalidomide: 15 mg orally on days 1-21; dexamethasone: 40 mg orally on days on days 1, 8, 15, 22.
Outcomes
Primary Outcome Measures
hematologic response rate
Secondary Outcome Measures
organ response rate
time to response
time to progression
survival
toxicity
Full Information
NCT ID
NCT00607581
First Posted
January 22, 2008
Last Updated
February 9, 2012
Sponsor
IRCCS Policlinico S. Matteo
Collaborators
Celgene Corporation
1. Study Identification
Unique Protocol Identification Number
NCT00607581
Brief Title
Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis
Official Title
An Open-label, Phase II Study of Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis
Study Type
Interventional
2. Study Status
Record Verification Date
February 2012
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Policlinico S. Matteo
Collaborators
Celgene Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The treatment of light-chain (AL) amyloidosis is directed against the plasma cells that produce the light-chain forming the amyloid deposits. The plasma cells can be killed and their growth can be stopped by drugs used in chemotherapy, such as cyclophosphamide, steroids, such as dexamethasone, and drugs that stimulate the immune system, such as lenalidomide.
The present trial studies the efficacy and safety of the combination of cyclophosphamide, lenalidomide and dexamethasone in patients with AL amyloidosis who were previously treated and need further therapy.
Detailed Description
This study will include previously treated patients with AL amyloidosis.
Primary objectives to determine the hematologic and organ response rate to the association of cyclophosphamide, lenalidomide and dexamethasone (CLD).
Secondary objectives
to determine the safety of CLD,
to determine time to response to CLD,
to determine the duration of response to CLD,
to assess survival of AL amyloidosis patients treated with CLD.
Patients receive 28-day cycles cyclophosphamide on days 1, 8 and 15, oral lenalidomide on days 1-21 and oral dexamethasone on days 1, 8, 15, and 22.
Up to 9 courses can be performed until one of the following endpoints is met:
completion of cycle 9,
complete hematologic remission observed after cycle 3 or 6,
partial hematologic response associated with organ response after cycle 6.
no response at cycle 3 or 6. After completion of study treatment, patients are followed every 3 months for up to 3 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis
Keywords
amyloidosis, lenalidomide, cyclophosphamide, dexamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
The participants receive up to 9 28-day cycles of
cyclophosphamide: 500 mg orally on days 1, 8, 15;
lenalidomide: 15 mg orally on days 1-21;
dexamethasone: 40 mg orally on days on days 1, 8, 15, 22.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Endoxan, D003520
Intervention Description
cyclophosphamide: 500 mg orally on days 1, 8, 15
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Revlimid, CC 5013, C467567
Intervention Description
lenalidomide: 15 mg orally on days 1-21
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Soldesam, D003907
Intervention Description
dexamethasone: 40 mg orally on days on days 1, 8, 15, 22
Primary Outcome Measure Information:
Title
hematologic response rate
Time Frame
at 3 months
Secondary Outcome Measure Information:
Title
organ response rate
Time Frame
at 3 months
Title
time to response
Time Frame
every 28 days
Title
time to progression
Time Frame
every 3 months for 3 years
Title
survival
Time Frame
up to 3 years after treatment discontinuation
Title
toxicity
Time Frame
continuous during treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Diagnosis of AL amyloidosis.
Evidence of a monoclonal light chain at serum and/or urine immunofixation electrophoresis.
Elevated circulating free light chain (of the type identified by immunofixation) above the upper limit of the normal range and abnormal kappa/lambda ratio.
Previously treated and requiring further treatment.
Symptomatic organ involvement.
Bone marrow plasma cell <30%.
Echocardiographic ejection fraction >40%.
Troponin I <0.1 ng/mL.
Hemoglobin >10 g/dL.
Absolute neutrophil count >1500/uL.
Platelet count >140000/uL.
Total bilirubin <2.5 mg/dL.
Alkaline phosphatase <4 x upper reference limit (u.r.l.).
ALT <3 x u.r.l..
Glomerular filtration rate >30 mL/min.
Performance status ECOG 1-3.
Female subjects of childbearing potential must have two negative pregnancy tests prior to starting study drug.
Exclusion Criteria:
Prior treatment with the association of cyclophosphamide, lenalidomide and dexamethasone or with lenalidomide.
Requirement for other concomitant chemotherapy, immunotherapy or radiotherapy, or any investigational ancillary therapy.
Presence of other active malignancies, with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limits.
Clinically overt multiple myeloma.
Uncontrolled infection.
New York Heart Association (NYHA) class 4 heart failure.
Enzyme documented myocardial infarction within 6 months before enrollment.
Grade 2 or 3 atrioventricular block (Mobitz type I is permitted).
Repetitive ventricular arrhythmias at 24 h Holter electrocardiogram in spite of treatment with amiodarone.
Supine systolic blood pressure <90 mmHg, or symptomatic orthostatic hypotension, or a decrease in systolic blood pressure on standing of >20 mmHg in spite of being treated for orthostatic hypotension.
Prior history of thrombosis or venous thromboembolism or pulmonary embolism. Prior diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency.
Indication to receive clopidogrel, ticlopidine or warfarin.
Factor X level <20%.
Poorly controlled diabetes mellitus (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months).
Previous or ongoing psychiatric illness (with the exclusion of reactive depression).
Pregnant or nursing women.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giampaolo Merlini, M.D.
Organizational Affiliation
Fondazione IRCCS Policlinico San Matteo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
16990593
Citation
Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007 Jan 15;109(2):457-64. doi: 10.1182/blood-2006-07-035352. Epub 2006 Sep 21.
Results Reference
background
PubMed Identifier
15572585
Citation
Palladini G, Perfetti V, Perlini S, Obici L, Lavatelli F, Caccialanza R, Invernizzi R, Comotti B, Merlini G. The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood. 2005 Apr 1;105(7):2949-51. doi: 10.1182/blood-2004-08-3231. Epub 2004 Nov 30.
Results Reference
background
PubMed Identifier
17008538
Citation
Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. doi: 10.1182/blood-2006-07-032987. Epub 2006 Sep 28.
Results Reference
background
PubMed Identifier
16960148
Citation
Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan 15;109(2):492-6. doi: 10.1182/blood-2006-07-030544. Epub 2006 Sep 7.
Results Reference
background
PubMed Identifier
16794250
Citation
Merlini G, Stone MJ. Dangerous small B-cell clones. Blood. 2006 Oct 15;108(8):2520-30. doi: 10.1182/blood-2006-03-001164. Epub 2006 Jun 22.
Results Reference
background
PubMed Identifier
22983583
Citation
Palladini G, Russo P, Milani P, Foli A, Lavatelli F, Nuvolone M, Perlini S, Merlini G. A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis. Haematologica. 2013 Mar;98(3):433-6. doi: 10.3324/haematol.2012.073593. Epub 2012 Sep 14.
Results Reference
derived
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Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis
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