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Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic 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: NCT00564889
Recruitment Status : Completed
First Posted : November 29, 2007
Results First Posted : August 12, 2011
Last Update Posted : May 14, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:

RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop plasma cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may be an effective treatment for primary systemic amyloidosis.

PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with primary systemic amyloidosis.

Condition or disease Intervention/treatment Phase
Multiple Myeloma and Plasma Cell Neoplasm Drug: cyclophosphamide Drug: dexamethasone Drug: lenalidomide Phase 2

Detailed Description:



* Assess the hematologic response rate in patients with primary systemic amyloidosis treated with lenalidomide, cyclophosphamide, and dexamethasone.


  • Determine the organ response rate in patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.
  • Determine the time to progression in patients treated with this regimen.
  • Determine the survival of patients treated with this regimen.

OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide* on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may receive cyclophosphamide for up to 1 year. After completion of study treatment, patients are followed every 6 months for up to 3 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis
Study Start Date : December 2007
Actual Primary Completion Date : February 2009
Actual Study Completion Date : June 2012

Arm Intervention/treatment
Experimental: CRD

Lenalidomide 15mg daily (days 1-21)

Cyclophosphamide 300 mg/m^2 (days 1, 8, 15)

Dexamethasone 40 mg weekly

Drug: cyclophosphamide
300 mg/m^2 days 1, 8 & 15 of a 28 day cycle taken orally with food

Drug: dexamethasone
40 mg weekly taken orally

Drug: lenalidomide
15 mg daily days 1-21 of a 28 day cycle taken orally with food

Primary Outcome Measures :
  1. Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) [ Time Frame: Duration on study (up to 3 years) ]

    Response that was confirmed on 2 consecutive evaluations during treatment.

    Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.

    Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.

    Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels.

Secondary Outcome Measures :
  1. Number of Patients With Organ Response [ Time Frame: Duration of study (up to 3 years) ]

    Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.

    Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%.

  2. Number of Participants With Severe Adverse Events [ Time Frame: Duration of study (up to 3 years) ]
    Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.

  3. Progression Free Survival (PFS) [ Time Frame: Duration of study (up to 3 years) ]
    Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.

  4. Overall Survival (OS) [ Time Frame: Duration of study (up to 3 years) ]
    Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

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


  • Histochemical diagnosis of AL amyloidosis based on detection of green birefringent material in Congo red-stained tissue specimens by polarizing microscopy
  • Measurable disease, as defined by one of the following:

    • Serum monoclonal protein ≥ 1.0 g by serum electrophoresis
    • Urine monoclonal protein > 200 mg by 24-hour urine electrophoresis
    • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • Symptomatic organ involvement with amyloid to justify therapy

    • May include liver involvement, cardiac involvement, renal involvement, grade 1 peripheral neuropathy, or soft tissue involvement
    • Must have more than skin purpura or carpal tunnel syndrome
  • No amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as only evidence of disease

    - Vascular amyloid only in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis

  • No clinically overt multiple myeloma (i.e., monoclonal BMPC > 30%, bone lesions, or hypercalcemia)


  • ECOG performance status 0-2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Creatinine < 3.0 mg/dL
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use two acceptable methods of contraception for ≥ 28 days prior to, during, and for ≥ 28 days after completion of study treatment
  • No nursing during and for ≥ 28 days after completion of study treatment
  • No blood, semen, or sperm donation during and for ≥ 28 days after completion of study treatment
  • No malignancies within the past 5 years except treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
  • No neuropathy ≥ grade 2, defined as motor neuropathy (symptomatic weakness interfering with function, but not interfering with activities of daily living [ADL]) or sensory neuropathy (sensory alteration or paresthesia [including tingling], interfering with function, but not interfering with ADL)
  • No uncontrolled infection
  • No syncope within the past 30 days
  • No known hypersensitivity to thalidomide, including desquamating rash with thalidomide in the past
  • No known seropositivity for HIV
  • No active hepatitis A, B, or C
  • No New York Heart Association class III or IV heart disease
  • No venous thromboembolic event within the past 42 days
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation - Patients intolerant to aspirin may use low molecular weight heparin


  • No prior lenalidomide
  • More than 2 weeks since prior and no other concurrent anticancer agents or treatments
  • More than 4 weeks since prior experimental agents
  • No other concurrent corticosteroids except chronic steroids (maximum dose 20 mg/day of prednisone equivalent) for disorders other than amyloidosis (e.g., adrenal insufficiency or rheumatoid arthritis)

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): NCT00564889

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United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
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Study Chair: Shaji K. Kumar, MD Mayo Clinic
Principal Investigator: Craig B. Reeder, MD Mayo Clinic
Principal Investigator: Vivek Roy, MD, FACP Mayo Clinic
Publications of Results:
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Responsible Party: Mayo Clinic Identifier: NCT00564889    
Other Study ID Numbers: MC0685
P30CA015083 ( U.S. NIH Grant/Contract )
MC0685 ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2010-01954 ( Other Identifier: NCI CTRP )
06-005711 ( Other Identifier: Mayo Clinic IRB )
First Posted: November 29, 2007    Key Record Dates
Results First Posted: August 12, 2011
Last Update Posted: May 14, 2013
Last Verified: April 2013
Keywords provided by Mayo Clinic:
primary systemic amyloidosis
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Immunoglobulin Light-chain Amyloidosis
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents