Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis - Full Text View

Sponsors and Collaborators:	IRCCS Policlinico S. Matteo Celgene Corporation
Information provided by:	IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:	NCT00607581

Purpose

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	Intervention	Phase
Amyloidosis	Drug: cyclophosphamide Drug: lenalidomide Drug: dexamethasone	Phase II

Drug Information available for: Cyclophosphamide Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Lenalidomide CC 5013

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	An Open-Label, Phase II Study of Cyclophosphamide, Lenalidomide and Dexamethasone (CLD) for Previously Treated Patients With AL Amyloidosis

Further study details as provided by IRCCS Policlinico S. Matteo:

Primary Outcome Measures:

hematologic response rate [ Time Frame: at 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

organ response rate [ Time Frame: at 3 months ] [ Designated as safety issue: No ]
time to response [ Time Frame: every 28 days ] [ Designated as safety issue: No ]
time to progression [ Time Frame: every 3 months for 3 years ] [ Designated as safety issue: No ]
survival [ Time Frame: up to 3 years after treatment discontinuation ] [ Designated as safety issue: No ]
toxicity [ Time Frame: continuous during treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	34
Study Start Date:	February 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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 Drug: lenalidomide lenalidomide: 15 mg orally on days 1-21 Drug: dexamethasone dexamethasone: 40 mg orally on days on days 1, 8, 15, 22

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607581

Contacts

Contact: Giovanni Palladini, M.D., Ph.D.

+39-0382-502621

g.palladini@smatteo.pv.it

Locations

Italy
Center for Amyloidosis - Fondazione IRCCS Policlinico San Matteo	Recruiting
Pavia, Italy, 27100
Contact: Giovanni Palladini, M.D., Ph.D. +39-0382-502621 g.palladini@smatteo.pv.it
Principal Investigator: Giampaolo Merlini, M.D.
Sub-Investigator: Giovanni Palladini, M.D., Ph.D.

Sponsors and Collaborators

IRCCS Policlinico S. Matteo

Celgene Corporation

Investigators

Principal Investigator:

Giampaolo Merlini, M.D.

Fondazione IRCCS Policlinico San Matteo

More Information

Publications:

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. Epub 2006 Sep 21.

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. Epub 2004 Nov 30.

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. Epub 2006 Sep 28.

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. Epub 2006 Sep 7.

Merlini G, Stone MJ. Dangerous small B-cell clones. Blood. 2006 Oct 15;108(8):2520-30. Epub 2006 Jun 22. Review.

Responsible Party:	Center for Amyloidosis - Fondazione IRCCS Policlinico S. Matteo ( Giampaolo Merlini )
Study ID Numbers:	AC-003-IT, RV-AMYL-PI-303
Study First Received:	January 22, 2008
Last Updated:	October 1, 2008
ClinicalTrials.gov Identifier:	NCT00607581
Health Authority:	Italy: Ethics Committee

Keywords provided by IRCCS Policlinico S. Matteo:

amyloidosis
lenalidomide
cyclophosphamide
dexamethasone

Study placed in the following topic categories:

Dexamethasone
Amyloidosis
Metabolic Diseases
Primary Amyloidosis

Lenalidomide
Cyclophosphamide
Metabolic disorder
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Hormones
Glucocorticoids

Immunosuppressive Agents
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009