Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma



Status:Active, not recruiting
Conditions:Hot Flash, Other Indications, Blood Cancer, Lymphoma, Anemia, Endocrine, Hematology
Therapuetic Areas:Endocrinology, Hematology, Oncology, Other, Reproductive
Healthy:No
Age Range:18 - 70
Updated:4/3/2019
Start Date:February 20, 2014

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A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients With Chronic Lymphocytic Leukemia (CLL)

This randomized phase III trial studies ibrutinib and rituximab to see how well they work
compared to fludarabine phosphate, cyclophosphamide, and rituximab in treating patients with
untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the
growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to
stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. Monoclonal antibodies, such as rituximab, interfere with
the ability of cancer cells to grow and spread. It is not yet known whether fludarabine
phosphate, cyclophosphamide, and rituximab may work better than ibrutinib and rituximab in
treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the ability of Ibrutinib-based induction therapy to prolong progression free
survival (PFS) compared to standard fludarabine phosphate, cyclophosphamide, and rituximab
(FCR) chemoimmunotherapy for younger patients with chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

I. Evaluate overall survival (OS) of patients based on treatment arm. II. Monitor and assess
toxicity of treatment with Ibrutinib-based induction relative to standard FCR chemotherapy.

III. To compare quality of life (QOL) in CLL patients during the first 6 months of treatment
among patients receiving Ibrutinib-based induction therapy relative to standard FCR
chemoimmunotherapy.

IV. To compare QOL over the long-term in CLL patients receiving continuous therapy using
Ibrutinib to that of CLL patients who completed FCR therapy.

V. Determine the effect of pretreatment clinical and biological characteristics (e.g. disease
stage, immunoglobulin heavy chain variable region gene [IGHV] mutation status, fluorescent in
situ hybridization [FISH]) on clinical outcomes (e.g. complete response, PFS) of the
different arms.

VI. Determine if the minimal residual disease (MRD) status as assessed by flow cytometry at
different time points during and after treatment is an effective surrogate marker for
prolonged PFS and overall survival.

VII. Compare the genetic abnormalities and dynamics of intra-clonal architecture of CLL
patients before and after treatment with chemoimmunotherapy (CIT) and non-CIT approaches and
explore relationships with treatment resistance.

VIII. Explore the effects of FCR and Ibrutinib-based therapy on T-cell immune function.

IX. Conduct confirmatory validation genotyping of single nucleotide polymorphisms (SNPs)
associated with the efficacy and toxicity of fludarabine-based therapy as in a prior Eastern
Cooperative Oncology Group (ECOG) genome-wide association study (GWAS) analysis in the E2997
trial.

X. Evaluate the ability of prognostic model that incorporates clinical and biologic
characters to predict a response to therapy and clinical outcome (PFS, OS).

XI. Evaluate signaling networks downstream of the B-cell receptor in patients receiving
Ibrutinib-based therapy.

XII. Collect relapse samples to study mechanisms of resistance to both FCR and
Ibrutinib-based therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning course
2, patients also receive rituximab intravenously (IV) over 4 hours on day 1 (days 1 and 2 of
course 2 only). Treatment repeats every 28 days for 7 courses. In the absence of disease
progression, patients may continue ibrutinib PO QD.

ARM B: Patients receive rituximab as seen in Arm A and fludarabine phosphate IV over 30
minutes and cyclophosphamide IV over 30 minutes on days 1-3. Treatment repeats every 28 days
for 6 courses.

After completion of study treatment, patients are followed up for 10 years.

Inclusion Criteria:

- Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on
Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL)
according to the World Health Organization (WHO) criteria; this includes previous
documentation of:

- Biopsy-proven small lymphocytic lymphoma or

- Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the
following:

- Peripheral blood lymphocyte count of greater than 5 x 10^9/L

- Immunophenotype consistent with CLL defined as:

- The predominant population of lymphocytes share both B-cell antigens
(cluster of differentiation [CD]19, CD20 [typically dim expression], or
CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3,
CD2, etc)

- Clonality as evidenced by kappa or lambda light chain restriction
(typically dim immunoglobulin expression)

- Negative FISH analysis for t(11;14)(immunoglobulin heavy locus [IgH]/cyclin D1
[CCND1]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative
immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g.
marrow aspirate or lymph node biopsy)

- No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal
anti-body therapy for treatment of CLL or SLL

- Has met at least one of the following indications for treatment:

- Evidence of progressive marrow failure as manifested by the development of
worsening anemia (hemoglobin [Hg] < 11 g/dl) and/or thrombocytopenia (platelets <
100 x 10^9/L)

- Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly

- One or more of the following disease-related symptoms:

- Weight loss >= 10% within the previous 6 months

- Grade 2 or 3 fatigue attributed to CLL

- Fevers > 100.5 Fahrenheit (F) for 2 weeks without evidence of infection

- Clinically significant night sweats without evidence of infection

- Progressive lymphocytosis (not due to the effects of corticosteroids) with an
increase of > 50% over a two-month period or an anticipated doubling time of less
than six months

- ECOG performance status between 0-2

- Life expectancy of >= 12 months

- Ability to tolerate FCR based therapy

- No deletion of 17p13 on cytogenetic analysis by FISH

- Glomerular filtration rate (GFR) > 40 mL/minute as calculated by the Cockcroft-Gault
formula

- Total bilirubin =< 2.5 x upper limit of normal (ULN) unless due to Gilbert's disease;
for those with a total bilirubin > 2.5 x ULN, a direct bilirubin should be performed
and must be < 1.5 mg/dL for Gilbert's to be diagnosed; if value is higher due to
hepatic involvement by CLL, patient is eligible

- Serum glutamic oxaloacetic transaminase (SGOT) aspartate transaminase (AST)/serum
glutamate-pyruvate transaminase (SGPT) alanine transaminase (ALT) =< 3.0 x the
institutional ULN; if value is higher due to hepatic involvement by CLL, patient is
eligible

- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 ULN and partial
thromboplastin time (PTT) activated partial thromboplastin time (aPTT) < 1.5 X ULN; if
value is higher due to hepatic involvement by CLL, patient is eligible

- No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic
treatment; patients who have a positive Coombs test but no evidence of hemolysis are
NOT excluded from participation

- No current use of corticosteroids; EXCEPTION: low doses of steroids (< 10 mg of
prednisone or equivalent dose of other steroid) used for treatment of non-hematologic
medical condition (e.g. chronic adrenal insufficiency) is permitted

- No previous use of corticosteroids for autoimmune complications that have developed
since the initial diagnosis of CLL; prior use of corticosteroids for reasons other
than treatment of autoimmune complications is allowed

- No other active primary malignancy (other than non-melanomatous skin cancer or
carcinoma in situ of the cervix) requiring treatment or limiting expected survival to
=< 2 years; NOTE: if there is a history of prior malignancy, they must not be
receiving other specific treatment (other than hormonal therapy for their cancer)

- Able to adhere to the study visit schedule and other protocol requirements

- No major surgery within the last 4 weeks (28 days) of first dose of study drug or
minor surgery within 3 days of first dose of study drug

- No radiation therapy =< 4 weeks prior to registration

- Patients with human immunodeficiency virus (HIV) infection may be eligible provided
they meet the following criteria:

- CD4-positive cell count >= lower limit of institutional normal

- HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL (if not on anti-HIV
therapy) OR < 50 copies HIV RNA/mL (if on anti-HIV therapy)

- No evidence of hepatitis B or C infection

- No evidence of resistant strains of HIV

- No history of acquired immune deficiency syndrome (AIDS)-defining condition

- Patients must not have any of the following conditions:

- Congestive heart failure or New York Heart Association Functional Classification
III or IV congestive heart failure

- History of myocardial infarction, unstable angina, or acute coronary syndrome
within 6 months prior to registration

- Recent infections requiring systemic treatment; need to have completed
anti-biotic therapy > 14 days before the first dose of study drug

- Cerebral vascular accident or intracranial bleed within the last 6 months

- Infection with known chronic, active hepatitis C

- Serologic status reflecting active hepatitis B or C infection; patients that are
positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or
hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior
to enrollment (PCR positive patients will be excluded)

- Patients are not eligible if they require treatment with a strong cytochrome P450
(CYP) family 3, subfamily A (3A) inhibitor

- Patients may not be on any other investigational agents

- Patients may not have received warfarin or another vitamin K antagonist in the
preceding 30 days

- Women must not be pregnant or breast-feeding; female patients of childbearing
potential must have a negative serum pregnancy test within 2 weeks prior to
registration to rule out pregnancy; female patients who are of non-reproductive
potential are those who are post-menopausal by history (i.e. no menses for >= 1 year);
OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of
bilateral oophorectomy

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for 90 days after the last dose of study drug

- Patient must be able to swallow capsules and not have the following conditions:

- Disease significantly affecting gastrointestinal function

- Resection of the stomach or small bowel

- Symptomatic inflammatory bowel disease

- Ulcerative colitis

- Partial or complete bowel obstruction

- Patient must not be on any other systemic immunosuppressant therapy other than
corticosteroids within 28 days of the first dose of study drug

- Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first
dose of study drug

- Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or
hemophilia

- Patient must not have currently active, clinically significant hepatic impairment (>=
moderate hepatic impairment according to the NCI/Child Pugh)
We found this trial at
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4755 Ogletown-Stanton Road
Newark, Delaware 19718
302-733-1000
Principal Investigator: Gregory A. Masters
Phone: 302-733-6227
Christiana Care Health System - Christiana Hospital A 913-bed, 1.3-million-square-foot, modern facility in Newark, Delaware,...
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1201 Camino de Salud Northeast
Albuquerque, New Mexico 87131
(505) 272-4946
Principal Investigator: Cecilia Y. Arana Yi
Phone: 505-925-0274
University of New Mexico Cancer Center It’s been 40 years since the New Mexico State...
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361 Old Belgrade Road
Augusta, Maine 04330
(207) 621-6100
Principal Investigator: Thomas H. Openshaw
Phone: 207-973-7807
Harold Alfond Center for Cancer Care MaineGeneral's Harold Alfond Center for Cancer Care (HACCC) is...
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2545 Schoenersville Rd
Bethlehem, Pennsylvania 18017
(484) 884-2200
Principal Investigator: Eliot L. Friedman
Phone: 610-402-2273
Lehigh Valley Hospital - Muhlenberg At Lehigh Valley Health Network, we continually go the extra...
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800 Washington St
Boston, Massachusetts 02111
(617) 636-5000
Principal Investigator: Andreas K. Klein
Phone: 617-636-5000
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
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Bremerton, Washington 98310
Principal Investigator: Mehmet S. Copur
Phone: 800-998-2119
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666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Seema A. Bhat
Phone: 716-845-3894
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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1 South Prospect Street
Burlington, Vermont 05401
802-656-8990
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1 Hurley Plaza
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(810) 262-9000
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200 North Park Street
Kalamazoo, Michigan 49007
(269) 382-2500
Principal Investigator: Sunil Nagpal
Phone: 269-373-7458
West Michigan Cancer Center In 1994, Borgess Health Alliance and Bronson Healthcare Group opened the...
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529 West Markham Street
Little Rock, Arkansas 72205
(501) 686-7000
Principal Investigator: Pooja Motwani
Phone: 501-686-8274
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777 Hemlock Street
Macon, Georgia 31201
(478) 633-1000
Principal Investigator: Frederick M. Schnell
Phone: 404-501-3279
Medical Center of Central Georgia Navicent Health is a designated Level I Trauma Center and...
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300 Community Drive
Manhasset, New York 11030
(516) 562-0100
Principal Investigator: Jacqueline C. Barrientos
Phone: 516-734-8954
North Shore University Hospital North Shore-LIJ Health System includes 16 award-winning hospitals and nearly 400...
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4805 Northeast Glisan Street
Portland, Oregon 97213
(503) 215-1111
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
Providence Portland Medical Center We strive to give those we serve exceptional, compassionate health care...
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401 College Street
Richmond, Virginia 23298
(804) 828-0450
Principal Investigator: Beata Holkova
Phone: 804-628-1939
Virginia Commonwealth University Massey Cancer Center Founded in 1974, VCU Massey Cancer Center is a...
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60 Crittenden Blvd # 70
Rochester, New York 14642
(585) 275-2121
Principal Investigator: Jonathan W. Friedberg
Phone: 585-275-5830
University of Rochester The University of Rochester is one of the country's top-tier research universities....
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4502 Medical Drive
San Antonio, Texas 78284
(210) 567-7000
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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Seattle, Washington 98104
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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1100 Fairview Avenue North
Seattle, Washington 98109
(206) 667-5000
Principal Investigator: Mazyar Shadman
Phone: 800-422-6237
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
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825 Eastlake Ave E
Seattle, Washington 98109
(206) 288-7222
Principal Investigator: Mazyar Shadman
Phone: 800-422-6237
Seattle Cancer Care Alliance Seattle Cancer Care Alliance (SCCA) is a cancer treatment center that...
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3900 W Avera Drive
Sioux Falls, South Dakota 57108
(605) 322-4700
Principal Investigator: Amy K. Krie
Phone: 605-322-6901
Avera Cancer Institute Avera, the health ministry of the Benedictine and Presentation Sisters, is a...
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808 North 39th Avenue
Yakima, Washington 98902
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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Aberdeen, Washington 98520
Principal Investigator: Keith S. Lanier
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Adrian, Michigan 49221
Principal Investigator: Rex B. Mowat
Phone: 800-444-3561
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818 Riverside Ave.
Adrian, Michigan 49221
(517) 265-0900
Bixby Medical Center ProMedica's Mission is to improve your health and well-being. Which is why,...
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1 Akron General Avenue
Akron, Ohio 44307
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Albany, Georgia 31701
Principal Investigator: Jose M. Tongol
Phone: 229-312-2251
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Albany, New York 12208
Principal Investigator: Charles H. Weissman
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Allentown, Pennsylvania 18103
Principal Investigator: Eliot L. Friedman
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Amarillo, Texas 79106
Principal Investigator: Stewart A. Sharp
Phone: 806-359-4673
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Ames, Iowa 50010
Principal Investigator: Joseph J. Merchant
Phone: 515-239-2621
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Ames, Iowa 50010
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Anaconda, Montana 59711
Principal Investigator: Benjamin T. Marchello
Phone: 800-648-6274
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Anacortes, Washington 98221
Principal Investigator: Keith S. Lanier
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Anaheim, California 92806
Principal Investigator: Jonathan A. Polikoff
Phone: 626-564-3455
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Anchorage, Alaska 99504
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
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Anchorage, Alaska 99508
Principal Investigator: Keith S. Lanier
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Anchorage, Alaska 98508
Principal Investigator: Keith S. Lanier
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Anderson, Indiana 46016
Principal Investigator: Ubaidullah Sharief
Phone: 765-646-8413
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5301 McAuley Drive
Ann Arbor, Michigan 48197
734-712-3456
Principal Investigator: Christopher M. Reynolds
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Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
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Ann Arbor, Michigan 48106
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Antigo, Wisconsin 54409
Principal Investigator: Hamied R. Rezazadeh
Phone: 877-405-6866
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Antioch, California 94531
Principal Investigator: Tatjana Kolevska
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921 North Oak Park Boulevard
Arroyo Grande, California 93420
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Asheville, North Carolina 28801
Principal Investigator: Christopher H. Chay
Phone: 828-418-0932
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Asheville, North Carolina 28801
Principal Investigator: Christopher H. Chay
Phone: 828-418-0932
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Asheville, North Carolina 28803
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Auburn, California 95602
Principal Investigator: Jorge A. Garcia-Young
Phone: 209-526-5280
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Auburn, California 95603
Principal Investigator: Jorge A. Garcia-Young
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Auburn, Washington 98001
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Aurora, Colorado 80012
Principal Investigator: Keren Sturtz
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1501 S Potomac St
Aurora, Colorado 80012
(303) 695-2600
Principal Investigator: Keren Sturtz
Phone: 303-777-2642
Medical Center of Aurora At The Medical Center of Aurora and Centennial Medical Plaza patients...
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2000 Ogden Ave
Aurora, Illinois 60504
(630) 978-6200
Principal Investigator: Maria T. Grosse-Perdekamp
Phone: 800-446-5532
Rush - Copley Medical Center Rush-Copley is proud to be the leading provider of health...
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Bainbridge Island, Washington 98110
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Baltimore, Maryland 21229
Principal Investigator: Carole B. Miller
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22 South Greene Street
Baltimore, Maryland 21201
410-328-7904
Principal Investigator: Seung-Tae Lee
Phone: 410-328-6896
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
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489 State St
Bangor, Maine 04401
(207) 973-7000
Principal Investigator: Thomas H. Openshaw
Phone: 207-973-7807
Eastern Maine Medical Center Located in Bangor, Eastern Maine Medical Center (EMMC) serves communities throughout...
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4305 New Shepherdsville Road
Bardstown, Kentucky 40004
Principal Investigator: Mehmet S. Copur
Phone: 800-998-2119
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Baton Rouge, Louisiana 70809
Principal Investigator: Robert V. Emmons
Phone: 888-562-4763
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Beachwood, Ohio 44122
Principal Investigator: Hillard M. Lazarus
Phone: 800-641-2422
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Beaver, Pennsylvania 15009
Principal Investigator: Alison R. Sehgal
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Bellevue, Washington 98004
Principal Investigator: John A. Keech
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Bellevue, Washington 98005
Principal Investigator: Keith S. Lanier
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Bellflower, California 90706
Principal Investigator: Jonathan A. Polikoff
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Bellingham, Washington 98225
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800 Farson Street
Belpre, Ohio 45714
(740) 401-0417
Principal Investigator: John P. Kuebler
Phone: 614-488-2745
Strecker Cancer Center-Belpre The Memorial Health System's Strecker Cancer Center, Belpre combines the clinical expertise...
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Bemidji, Minnesota 56601
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Bend, Oregon 97701
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Berkeley, California 94704
Principal Investigator: Jorge A. Garcia-Young
Phone: 209-526-5280
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Berkeley, CA
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Berlin, VT
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Beverly, Massachusetts 01915
Principal Investigator: Angus P. McIntyre
Phone: 978-283-4000
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Beverly, MA
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Billings, Montana 59101
Principal Investigator: Benjamin T. Marchello
Phone: 800-648-6274
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Billings, MT
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Billings, Montana 59101
Principal Investigator: Benjamin T. Marchello
Phone: 800-648-6274
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Billings, MT
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1233 North 30th Street
Billings, Montana 59101
406-237-7000
Principal Investigator: Benjamin T. Marchello
Phone: 800-648-6274
Saint Vincent Healthcare The Sisters of Charity of Leavenworth, Kansas, founded St. Vincent Healthcare in...
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Billings, MT
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Birmingham, Alabama 35233
Principal Investigator: Harry P. Erba
Phone: 205-934-0309
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Birmingham, AL
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300 N. Seventh St.
Bismarck, North Dakota 58501
(701) 323-6000
Principal Investigator: Preston D. Steen
Phone: 701-234-6161
Sanford Bismarck Medical Center Whether your stay in our hospital is one day for same...
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Bismarck, ND
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Bloomington, Illinois 61701
Principal Investigator: James L. Wade
Phone: 217-876-4740
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Bloomington, IL
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1505 Eastland Drive
Bloomington, Illinois 61701
309-662-2102
Principal Investigator: James L. Wade
Phone: 217-876-4740
Illinois CancerCare-Bloomington Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood diseases. Our...
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Bloomington, IL
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Boise, Idaho 83706
Principal Investigator: Christopher M. Reynolds
Phone: 734-712-4673
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Boise, ID
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100 E Idaho St
Boise, Idaho 83712
(208) 381-2711
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
Saint Luke's Mountain States Tumor Institute For more than 100 years, St. Luke
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Boise, ID
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Bolivar, Missouri 65613
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Bolivar, MO
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Bonne Terre, Missouri 63628
Principal Investigator: James L. Wade
Phone: 217-876-4740
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Bonne Terre, MO
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Boone, Iowa 50036
Principal Investigator: Joseph J. Merchant
Phone: 515-239-2621
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Boone, IA
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Boston, Massachusetts 02215
Principal Investigator: Tait D. Shanafelt
Phone: 507-284-2358
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Boston, MA
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1100 Balsam Ave
Boulder, Colorado 80304
(303) 440-2273
Principal Investigator: Keren Sturtz
Phone: 303-777-2642
Boulder Community Hospital Founded in 1922 as a community-owned and operated not-for-profit hospital, Boulder Community...
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Boulder, CO
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Boulder, Colorado 80303
Principal Investigator: Keren Sturtz
Phone: 303-777-2642
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Boulder, CO
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960 W Wooster St
Bowling Green, Ohio 43402
419-353-5419
Toledo Clinic Cancer Centers-Bowling Green Our doctors evaluate and make recommendations regarding cancer treatment for...
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Bowling Green, OH
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915 Highland Blvd
Bozeman, Montana 59715
(406) 414-5000
Principal Investigator: Benjamin T. Marchello
Phone: 800-648-6274
Bozeman Deaconess Hospital Bozeman Deaconess Hospital is a Joint Commission certified, licensed Level III trauma...
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Bozeman, MT
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Brainerd, Minnesota 56401
Principal Investigator: Bret E. Friday
Phone: 888-203-7267
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Brainerd, MN
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Branson, Missouri 65616
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Branson, MO
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Bremerton, Washington 98310
Principal Investigator: Mehmet S. Copur
Phone: 800-998-2119
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Bremerton, WA
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Brewer, Maine 04412
Principal Investigator: Thomas H. Openshaw
Phone: 207-973-7807
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Brewer, ME
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