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

February 9, 2012 updated by: Giampaolo Merlini, IRCCS Policlinico S. Matteo

An Open-label, Phase II Study of Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
hematologic response rate
Time Frame: at 3 months
at 3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
organ response rate
Time Frame: at 3 months
at 3 months
time to response
Time Frame: every 28 days
every 28 days
time to progression
Time Frame: every 3 months for 3 years
every 3 months for 3 years
survival
Time Frame: up to 3 years after treatment discontinuation
up to 3 years after treatment discontinuation
toxicity
Time Frame: continuous during treatment
continuous during treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Matteo

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: Giampaolo Merlini, M.D., Fondazione IRCCS Policlinico San Matteo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

January 22, 2008

First Submitted That Met QC Criteria

January 22, 2008

First Posted (Estimate)

February 5, 2008

Study Record Updates

Last Update Posted (Estimate)

February 10, 2012

Last Update Submitted That Met QC Criteria

February 9, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-003-IT
  • RV-AMYL-PI-303

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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