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

NCT00607581 | Completed Phase 2

• 2 other identifiers: AC-003-ITRV-AMYL-PI-303
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyloidosis

Keywords

amyloidosis; lenalidomide; cyclophosphamide; dexamethasone

Outcome Measures

Primary Outcomes (1)

• hematologic response rate

  at 3 months

Secondary Outcomes (5)

• organ response rate

  at 3 months

• time to response

  every 28 days

• time to progression

  every 3 months for 3 years

• survival

  up to 3 years after treatment discontinuation

• toxicity

  continuous during treatment

Study Arms (1)

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; Drug: lenalidomide; Drug: dexamethasone

Interventions

cyclophosphamide DRUG

cyclophosphamide: 500 mg orally on days 1, 8, 15

Also known as: Endoxan, D003520

1

lenalidomide DRUG

lenalidomide: 15 mg orally on days 1-21

Also known as: Revlimid, CC 5013, C467567

1

dexamethasone DRUG

dexamethasone: 40 mg orally on days on days 1, 8, 15, 22

Also known as: Soldesam, D003907

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Pregnant or nursing women.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead
• Celgene Corporation: collaborator

Study Sites (1)

Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, 27100, Italy

Location

Related Publications (6)

• 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.

  PMID: 16990593 BACKGROUND

• 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.

  PMID: 15572585 BACKGROUND

• 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.

  PMID: 17008538 BACKGROUND

• 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.

  PMID: 16960148 BACKGROUND

• 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.

  PMID: 16794250 BACKGROUND

• 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.

  PMID: 22983583 DERIVED

MeSH Terms

Conditions

Amyloidosis

Interventions

Cyclophosphamide; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Giampaolo Merlini, M.D.

  Fondazione IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Amyloidosis Treatment and Research Center

Study Record Dates

• First Submitted: January 22, 2008
• First Posted: February 5, 2008
• Study Start: February 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: February 10, 2012

Record last verified: 2012-02

Locations

IT (1)