NCT00060346

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed Waldenstrom's macroglobulinemia.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_2 lymphoma

Timeline
Completed

Started Oct 2004

Typical duration for phase_2 lymphoma

Geographic Reach
1 country

153 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 7, 2003

Completed
1.4 years until next milestone

Study Start

First participant enrolled

October 5, 2004

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2011

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2012

Completed
7 months until next milestone

Results Posted

Study results publicly available

February 12, 2013

Completed
Last Updated

June 29, 2023

Status Verified

June 1, 2023

Enrollment Period

7.2 years

First QC Date

May 6, 2003

Results QC Date

January 10, 2013

Last Update Submit

June 14, 2023

Conditions

Keywords

Waldenstrom macroglobulinemiaRituximabCHOP

Outcome Measures

Primary Outcomes (1)

  • Objective Response to Treatment

    Objective response assessed using standard myeloma response criteria. Objective response is defined as a \> 50% reduction in the quantitative IgM or M-Spike levels from baseline levels. Response must be documented by two measurements separated by at least 3 weeks.

    Every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry

Study Arms (1)

Rituximab + CHOP

EXPERIMENTAL

Rituximab 375 mg/m2 day 1 of a 21-day cycle, followed by: Cyclophosphamide 750 mg/m2 Doxorubicin 50 mg/m2 Vincristine 1.4 mg/m2 and Prednisone 100 mg/m2 daily

Biological: rituximabDrug: cyclophosphamideDrug: DoxorubicinDrug: PrednisoneDrug: Vincristine

Interventions

rituximabBIOLOGICAL

Rituximab is given intravenously. The initial rate is 50 mg/hr for the 1st hour. If no toxicity, the rate may be escalated in 50 mg/hr increments at 30-minute intervals to a maximum of 400 mg/hr. If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr. If the patient experiences fever and rigors, the antibody infusion is discontinued. The severity of the side effects should be evaluated. If the symptoms improve, the infusion is continued initially at half the previous rate. Following the antibody infusion, the intravenous line should be maintained for medications as needed. If there are no complications after one hour of observation, the intravenous line may be discontinued.

Also known as: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan, NSC# 687451
Rituximab + CHOP

Cyclophosphamide will be given at a dosage of 750 mg/m² intravenously on day 1 of each cycle (1 cycle =21 days) for 6 cycles. Dose is based on surface area calculated based on actual body weight. The drug should be administered as a rapid IV infusion over 5 to 30 minutes.

Also known as: Cytoxan, CTX, CPM, Neosar
Rituximab + CHOP

Doxorubicin will be given intravenously at a dosage of 50 mg/m² on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight. Doxorubicin should be administered as a continuous infusion into tubing of a freely flowing intravenous line for 5 -15 minutes. Avoid extravasation.

Also known as: Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS, hydroxydaunorubicin, ADR
Rituximab + CHOP

Prednisone will be administered at 100 mg/m² orally, days 1-5 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.

Also known as: Deltasone, Orasone, Medicortone, Panasol-S, Liqui-Pred
Rituximab + CHOP

Vincristine will be administered 1.4 mg/m² intravenously (Maximum dose = 2.0 mg) on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight. Given as IV push over 1 minute, using extravasation precautions.

Also known as: Vinsacar PFS, vincristine sulfate, VCR, leucocristine, LCR
Rituximab + CHOP

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of Waldenstrom's macroglobulinemia confirmed by the presence of the following:
  • Bone marrow lymphoplasmacytosis with: \> 10% lymphoplasmacytic cells OR aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 4 weeks prior to registration)
  • Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal protein of \> 1,000 mg/dL obtained within 4 weeks prior to registration
  • Cluster of differentiation 20 (CD20) positive stain of bone marrow or lymph node samples obtained \< 8 weeks prior to registration
  • Impaired bone marrow function due to infiltration by lymphoplasmacytic lymphoma, defined by 1 of the following:
  • Hemoglobin no greater than 11 g/dL
  • Serum viscosity level relative to water of at least 4.0 centipoise
  • Absolute neutrophil count at least 1,000/mm\^3
  • Platelet count at least 75,000/mm\^3
  • Bilirubin no greater than 3.0 mg/dL
  • Aspartate aminotransferase (AST) no greater than 3 times upper limit of normal
  • Creatinine no greater than 3.0 mg/dL
  • Age of 18 and over
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Must be symptomatic with 1 of the following:
  • +9 more criteria

You may not qualify if:

  • Prior treatment for Waldenstrom's macroglobulinemia
  • Prior anti-CD20 therapy
  • Concurrent steroids exceeding 10 mg prednisone (or equivalent) per day
  • Prior irradiation if less than 4 weeks had elapsed prior to registration and the date of last treatment
  • Prior anthracyclines
  • Prior malignancy except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer curatively treated with surgery alone and from which patient has been disease free for at least 5 years
  • Active heart disease
  • Pregnant or nursing
  • Myocardial infarction within the past 3 months
  • Congestive heart failure
  • Symptomatic ventricular arrhythmia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (153)

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Rush-Copley Cancer Care Center

Aurora, Illinois, 60507, United States

Location

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, 60435, United States

Location

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, 46107, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

William N. Wishard Memorial Hospital

Indianapolis, Indiana, 46202, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

Saint Anthony Memorial Health Centers

Michigan City, Indiana, 46360, United States

Location

Reid Hospital & Health Care Services, Incorporated

Richmond, Indiana, 47374, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Saint Joseph Regional Medical Center

South Bend, Indiana, 46617, United States

Location

McFarland Clinic, PC

Ames, Iowa, 50010, United States

Location

Genesis Regional Cancer Center at Genesis Medical Center

Davenport, Iowa, 52803, United States

Location

Genesis Medical Center - West Campus

Davenport, Iowa, 52804, United States

Location

Mercy Capitol Hospital

Des Moines, Iowa, 50307, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

John Stoddard Cancer Center

Des Moines, Iowa, 50316-2301, United States

Location

Mercy Cancer Center at Mercy Medical Center - North Iowa

Mason City, Iowa, 50401, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51104, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Medical Oncology and Hematology Associates - West Des Moines

West Des Moines, Iowa, 50266, United States

Location

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, 66720, United States

Location

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, 67801, United States

Location

Cancer Center of Kansas, PA - El Dorado

El Dorado, Kansas, 67042, United States

Location

Cancer Center of Kansas, PA - Kingman

Kingman, Kansas, 67068, United States

Location

Southwest Medical Center

Liberal, Kansas, 67901, United States

Location

Cancer Center of Kansas, PA - Newton

Newton, Kansas, 67114, United States

Location

Cancer Center of Kansas, PA - Parsons

Parsons, Kansas, 67357, United States

Location

Cancer Center of Kansas, PA - Pratt

Pratt, Kansas, 67124, United States

Location

Cancer Center of Kansas, PA - Salina

Salina, Kansas, 67042, United States

Location

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

Cotton-O'Neil Cancer Center

Topeka, Kansas, 66604, United States

Location

St. Francis Comprehensive Cancer Center

Topeka, Kansas, 66606, United States

Location

Cancer Center of Kansas, PA - Wellington

Wellington, Kansas, 67152, United States

Location

Associates in Womens Health, PA - North Review

Wichita, Kansas, 67203, United States

Location

Cancer Center of Kansas, PA - Medical Arts Tower

Wichita, Kansas, 67208, United States

Location

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, 67214, United States

Location

CCOP - Wichita

Wichita, Kansas, 67214, United States

Location

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

Cancer Center of Kansas, PA - Winfield

Winfield, Kansas, 67156, United States

Location

Union Hospital Cancer Program at Union Hospital

Elkton, Maryland, 21921, United States

Location

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, 49017, United States

Location

Mecosta County Medical Center

Big Rapids, Michigan, 49307, United States

Location

CCOP - Grand Rapids

Grand Rapids, Michigan, 49503, United States

Location

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

Metro Health Hospital

Grand Rapids, Michigan, 49506, United States

Location

Holland Community Hospital

Holland, Michigan, 49423, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Hackley Hospital

Muskegon, Michigan, 49442, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

MeritCare Bemidji

Bemidji, Minnesota, 56601, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

Meeker County Memorial Hospital

Litchfield, Minnesota, 55355, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

HealthEast Cancer Care at St. Joseph's Hospital

Saint Paul, Minnesota, 55102, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

HealthEast Cancer Care at Woodwinds Health Campus

Woodbury, Minnesota, 55125, United States

Location

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Saint Louis University Cancer Center

St Louis, Missouri, 63110, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, 59101, United States

Location

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101, United States

Location

St. Vincent Healthcare Cancer Care Services

Billings, Montana, 59101, United States

Location

Billings Clinic Cancer Center

Billings, Montana, 59107-5100, United States

Location

Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Bozeman Deaconess Cancer Center

Bozeman, Montana, 59715, United States

Location

St. James Healthcare Cancer Care

Butte, Montana, 59701, United States

Location

Great Falls Clinic - Main Facility

Great Falls, Montana, 59405, United States

Location

Great Falls Clinic

Great Falls, Montana, 59405, United States

Location

St. Peter's Hospital

Helena, Montana, 59601, United States

Location

Glacier Oncology, PLLC

Kalispell, Montana, 59901, United States

Location

Kalispell Medical Oncology at KRMC

Kalispell, Montana, 59901, United States

Location

Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

Community Medical Center

Missoula, Montana, 59801, United States

Location

Guardian Oncology and Center for Wellness

Missoula, Montana, 59804, United States

Location

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, 59807-7877, United States

Location

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, 59807, United States

Location

Hunterdon Regional Cancer Center at Hunterdon Medical Center

Flemington, New Jersey, 08822, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, 08053, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua West Jersey

Voorhees Township, New Jersey, 08043, United States

Location

Interlakes Oncology/Hematology PC

Rochester, New York, 14623, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Our Lady of Mercy Medical Center Comprehensive Cancer Center

The Bronx, New York, 10466, United States

Location

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, 27534, United States

Location

Wayne Radiation Oncology

Goldsboro, North Carolina, 27534, United States

Location

Rutherford Hospital

Rutherfordton, North Carolina, 28139, United States

Location

Wilson Medical Center

Wilson, North Carolina, 27893-3428, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

MeritCare Broadway

Fargo, North Dakota, 58122, United States

Location

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, 44710-1799, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital

Dayton, Ohio, 45406, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Samaritan North Cancer Care Center

Dayton, Ohio, 45415, United States

Location

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, 45428, United States

Location

CCOP - Dayton

Dayton, Ohio, 45429, United States

Location

Community Oncology Group at Cleveland Clinic Cancer Center

Independence, Ohio, 44131, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

St. Rita's Medical Center

Lima, Ohio, 45801, United States

Location

Middletown Regional Hospital

Middletown, Ohio, 45044, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

Cleveland Clinic - Wooster

Wooster, Ohio, 44691, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-0001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Lewistown Hospital

Lewistown, Pennsylvania, 17044, United States

Location

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, 16801, United States

Location

Mount Nittany Medical Center

State College, Pennsylvania, 16803, United States

Location

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, 18711, United States

Location

AnMed Cancer Center

Anderson, South Carolina, 29621, United States

Location

CCOP - Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Medical X-Ray Center, PC

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Wilford Hall Medical Center

Lackland Air Force Base, Texas, 78236, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Danville Regional Medical Center

Danville, Virginia, 24541, United States

Location

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, 82801, United States

Location

Related Publications (1)

  • Abonour R, Zhang LA, Rajkumar V, et al.: Phase II pilot study of rituximab + CHOP in patients with newly diagnosed Waldenstroms macroglobulinemia, an Eastren Cooperative Oncology Group trial (study E1A02). [Abstract] Blood 110 (11): A-3616, 2007.

    RESULT

MeSH Terms

Conditions

LymphomaWaldenstrom Macroglobulinemia

Interventions

RituximabCyclophosphamideDoxorubicinPrednisoneVincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizines

Results Point of Contact

Title
Study Statistician
Organization
ECOG Statistical Office

Study Officials

  • Rafat Abonour, MD

    Indiana University Melvin and Bren Simon Cancer Center

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

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

Study Record Dates

First Submitted

May 6, 2003

First Posted

May 7, 2003

Study Start

October 5, 2004

Primary Completion

December 1, 2011

Study Completion

August 1, 2012

Last Updated

June 29, 2023

Results First Posted

February 12, 2013

Record last verified: 2023-06

Locations