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

NCT00564889 | Completed Phase 2 Results

• 4 other identifiers: MC0685P30CA015083NCI-2010-0195406-005711
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

primary systemic amyloidosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)

  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 Outcomes (4)

• Number of Patients With Organ Response

  Duration of study (up to 3 years)

• Number of Participants With Severe Adverse Events

  Duration of study (up to 3 years)

• Progression Free Survival (PFS)

  Duration of study (up to 3 years)

• Overall Survival (OS)

  Duration of study (up to 3 years)

Study Arms (1)

CRD

EXPERIMENTAL

Lenalidomide 15mg daily (days 1-21) Cyclophosphamide 300 mg/m\^2 (days 1, 8, 15) Dexamethasone 40 mg weekly

Drug: cyclophosphamide; Drug: dexamethasone; Drug: lenalidomide

Interventions

cyclophosphamide DRUG

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

CRD

dexamethasone DRUG

40 mg weekly taken orally

CRD

lenalidomide DRUG

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

CRD

Eligibility Criteria

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

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 22504925 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis

Interventions

Cyclophosphamide; Dexamethasone; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; 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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Shaji Kumar
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

Study Officials

• Shaji K. Kumar, MD

  Mayo Clinic

  STUDY CHAIR

• Craig B. Reeder, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Vivek Roy, MD, FACP

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2007
• First Posted: November 29, 2007
• Study Start: December 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: June 1, 2012
• Last Updated: May 14, 2013
• Results First Posted: August 12, 2011

Record last verified: 2013-04

Locations

US (3)