Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis

April 10, 2013 updated by: Mayo Clinic

A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

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

Secondary

  • 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.

Study Type

Interventional

Enrollment (Actual)

35

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

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259-5499
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

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

DISEASE CHARACTERISTICS:

  • 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)

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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)

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Duration on study (up to 3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%.
Duration of study (up to 3 years)
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.
Duration of study (up to 3 years)
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.
Duration of study (up to 3 years)
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.
Duration of study (up to 3 years)

Collaborators and Investigators

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

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • 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 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

December 1, 2007

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

November 28, 2007

First Submitted That Met QC Criteria

November 28, 2007

First Posted (Estimate)

November 29, 2007

Study Record Updates

Last Update Posted (Estimate)

May 14, 2013

Last Update Submitted That Met QC Criteria

April 10, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC0685 (Other Identifier: Mayo Clinic Cancer Center)
  • P30CA015083 (U.S. NIH Grant/Contract)
  • NCI-2010-01954 (Other Identifier: NCI CTRP)
  • 06-005711 (Other Identifier: Mayo Clinic IRB)

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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