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Trial record 6 of 23 for:    "Al Amyloidosis" | "Cyclophosphamide"

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

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ClinicalTrials.gov Identifier: NCT00564889
Recruitment Status : Completed
First Posted : November 29, 2007
Results First Posted : August 12, 2011
Last Update Posted : May 14, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE November 28, 2007
First Posted Date  ICMJE November 29, 2007
Results First Submitted Date  ICMJE July 19, 2011
Results First Posted Date  ICMJE August 12, 2011
Last Update Posted Date May 14, 2013
Study Start Date  ICMJE December 2007
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2011)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2007)
Hematologic response rate at 3 months
Change History Complete list of historical versions of study NCT00564889 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2013)
  • 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%.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2007)
  • Organ response rate
  • Toxicity
  • Time to progression
  • Survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis
Official Title  ICMJE A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: CRD

Lenalidomide 15mg daily (days 1-21)

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

Dexamethasone 40 mg weekly

Interventions:
  • Drug: cyclophosphamide
  • Drug: dexamethasone
  • Drug: lenalidomide
Publications * Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7. doi: 10.1182/blood-2012-01-407791. Epub 2012 Apr 13.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 28, 2007)
35
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00564889
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Shaji K. Kumar, MD Mayo Clinic
Principal Investigator: Craig B. Reeder, MD Mayo Clinic
Principal Investigator: Vivek Roy, MD, FACP Mayo Clinic
PRS Account Mayo Clinic
Verification Date April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP