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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Giampaolo Merlini, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:
NCT00607581
First received: January 22, 2008
Last updated: February 9, 2012
Last verified: February 2012
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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 ]

Enrollment: 21
Study Start Date: February 2008
Study Completion Date: January 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Italy
Amyloidosis Research and Treatment Center - Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
Celgene Corporation
Investigators
Principal Investigator: Giampaolo Merlini, M.D. Fondazione IRCCS Policlinico San Matteo
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Giampaolo Merlini, Director, Amyloidosis Treatment and Research Center, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT00607581     History of Changes
Other Study ID Numbers: AC-003-IT, RV-AMYL-PI-303
Study First Received: January 22, 2008
Last Updated: February 9, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS Policlinico S. Matteo:
amyloidosis
lenalidomide
cyclophosphamide
dexamethasone

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Cyclophosphamide
Thalidomide
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 16, 2014