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Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00607581
Recruitment Status : Completed
First Posted : February 5, 2008
Last Update Posted : February 10, 2012
Celgene Corporation
Information provided by (Responsible Party):
Giampaolo Merlini, IRCCS Policlinico S. Matteo

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.

Condition or disease Intervention/treatment Phase
Amyloidosis Drug: cyclophosphamide Drug: lenalidomide Drug: dexamethasone Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Phase II Study of Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis
Study Start Date : February 2008
Actual Primary Completion Date : December 2011
Actual Study Completion Date : January 2012

Arm Intervention/treatment
Experimental: 1

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.
Drug: cyclophosphamide
cyclophosphamide: 500 mg orally on days 1, 8, 15
Other Names:
  • Endoxan
  • D003520

Drug: lenalidomide
lenalidomide: 15 mg orally on days 1-21
Other Names:
  • Revlimid
  • CC 5013
  • C467567

Drug: dexamethasone
dexamethasone: 40 mg orally on days on days 1, 8, 15, 22
Other Names:
  • Soldesam
  • D003907

Primary Outcome Measures :
  1. hematologic response rate [ Time Frame: at 3 months ]

Secondary Outcome Measures :
  1. organ response rate [ Time Frame: at 3 months ]
  2. time to response [ Time Frame: every 28 days ]
  3. time to progression [ Time Frame: every 3 months for 3 years ]
  4. survival [ Time Frame: up to 3 years after treatment discontinuation ]
  5. toxicity [ Time Frame: continuous during treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00607581

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Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
Celgene Corporation
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Principal Investigator: Giampaolo Merlini, M.D. Fondazione IRCCS Policlinico San Matteo
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Giampaolo Merlini, Director, Amyloidosis Treatment and Research Center, IRCCS Policlinico S. Matteo Identifier: NCT00607581    
Other Study ID Numbers: AC-003-IT
First Posted: February 5, 2008    Key Record Dates
Last Update Posted: February 10, 2012
Last Verified: February 2012
Keywords provided by Giampaolo Merlini, IRCCS Policlinico S. Matteo:
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents