Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)

NCT ID: NCT00391066

Last Updated: 2015-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

627 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-30

Study Completion Date

2010-12-31

Brief Summary

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This is a randomized (1:1), open-label, multicenter, active-controlled study in patients with previously treated CD23+ and CD20+ relapsed CLL. Patients will receive treatment with either lumiliximab in combination with FCR or FCR alone.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

FCR

F (Fludarabine): 25 mg/m2 daily, every four weeks for 21 weeks

C (Cyclophosphamide): 250 mg/m2 daily, every four weeks for 21 weeks

R: (Rituximab): Day 1 50 mg/m2, Day 3 325 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks

Group Type ACTIVE_COMPARATOR

FCR

Intervention Type DRUG

Dose, schedule, and duration specified in protocol

2

FCR + Lumiliximab (L)

L (Lumiliximab): Day 2 50 mg/m2, Day 4 450 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks.

F (Fludarabine): 25 mg/m2 daily, every four weeks for 21 weeks

C (Cyclophosphamide): 250 mg/m2 daily, every four weeks for 21 weeks

R: (Rituximab): Day 1 50 mg/m2, Day 3 325 mg/m2, for the first week, then single doses of 500 mg/m2 every four weeks, for 21 weeks

Group Type EXPERIMENTAL

FCR + Lumiliximab

Intervention Type DRUG

Dose, schedule, and duration specified in the protocol

Interventions

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FCR + Lumiliximab

Dose, schedule, and duration specified in the protocol

Intervention Type DRUG

FCR

Dose, schedule, and duration specified in protocol

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed, written EC-approved informed consent form.
* Diagnosis of relapsed CD23+ and CD20+ B cell CLL as defined by NCI WG guidelines.
* Subjects who have received at least 1 but no more than 2 prior single agent or combination treatments for CLL.
* Rai Stage III or IV (Binet Stage C), or Rai Stage I or II (Binet Stage A or B) if determined to have disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms (Staging Criteria - Modified Rai).
* WHO Performance Status less than or equal to 2.
* Age greater than or equal to 18 years.
* Male and female subjects of reproductive potential must agree to follow accepted birth control methods during treatment and for 12 months after completion of treatment.
* Acceptable liver function: bilirubin less than or equal to 2.0 mg/dL (26 µmol/L); AST and ALT less than or equal to 2 times upper limit of normal.
* Acceptable hematologic status: platelet count greater than or equal to 50 x 10\^9/L should be unsupported by transfusion; ANC greater than or equal to 1 x 10\^9/L.
* Acceptable renal function: creatinine clearance calculated according to the formula of Cockcroft and Gault \>50 mL/min; serum creatinine less than or equal to 1.5 times upper limit of normal.

Exclusion Criteria

* Subjects who are refractory to the following combination therapies: purine analogue + R, purine analogue + C, or purine analogue + CR. Refractory is defined as not achieving at least a PR for a minimum duration of 6 months as determined by treating physician. Purine analogues include fludarabine, pentostatin and cladribine.
* Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other investigational therapy within 4 weeks prior to Study Day 1.
* Previous exposure to lumiliximab or other anti-CD23 antibodies.
* Prior autologous or allogeneic BMT or hematopoetic stem cell transplant.
* Known infection with HIV, hepatitis B, or hepatitis C. Although testing for hepatitis B or hepatitis C is not mandatory, this should be considered for all subjects considered at high risk of hepatitis B or hepatitis C infection and in endemic areas. Subjects with any serological evidence of current or past hepatitis B or hepatitis C exposure are excluded unless the serological findings are clearly due to vaccination.
* Uncontrolled diabetes mellitus.
* Uncontrolled hypertension.
* Transformation to aggressive B-cell malignancy (e.g., large B cell lymphoma, Richter's Syndrome, or PLL).
* Secondary malignancy requiring active treatment (except hormonal therapy).
* Any medical condition that would require long-term use (\>1 month) of systemic corticosteroids during study treatment. However, steroid use less than or equal to 1 month is permissible during the study.
* Any serious nonmalignant disease or laboratory abnormality, which in the opinion of the Investigator and/or Sponsor would compromise protocol objectives.
* Active uncontrolled bacterial, viral, or fungal infections.
* New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months prior to Study Day 1, unstable arrhythmia, or evidence of ischemia on ECG within 30 days prior to Study Day 1.
* Seizure disorders requiring anticonvulsant therapy.
* Severe chronic obstructive pulmonary disease with hypoxemia.
* Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1.
* Clinically active autoimmune disease.
* History of fludarabine-induced autoimmune cytopenia (as judged by the Investigator) or Coombs-positive haemolytic anemia.
* Pregnant or currently breastfeeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

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Scottsdale, Arizona, United States

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Alhambra, California, United States

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Burbank, California, United States

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Fullerton, California, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Northridge, California, United States

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Oxnard, California, United States

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Pomona, California, United States

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Redondo Beach, California, United States

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Sacramento, California, United States

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Santa Maria, California, United States

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Fort Myers, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Chicago, Illinois, United States

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Maywood, Illinois, United States

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Indianapolis, Indiana, United States

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Overland Park, Kansas, United States

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Shreveport, Louisiana, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Saint Joseph, Michigan, United States

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Ypsilant,, Michigan, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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St Louis, Missouri, United States

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Billings, Montana, United States

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Omaha, Nebraska, United States

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Hackensack, New Jersey, United States

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Morristown, New Jersey, United States

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Chapel Hill, North Carolina, United States

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Raleigh, North Carolina, United States

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Columbus, Ohio, United States

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Kettering, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Fredericksburg, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Norfolk, Virginia, United States

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Roanoke, Virginia, United States

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Kennewick, Washington, United States

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Saint Louis, Washington, United States

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Spokane, Washington, United States

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Yakima, Washington, United States

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Córdoba, , Argentina

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Mendoza, , Argentina

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Darlinghurst, New South Wales, Australia

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Gosford, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Waratah, New South Wales, Australia

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Westmead, New South Wales, Australia

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Greenslopes, Queensland, Australia

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Herston, Queensland, Australia

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South Brisbane, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Adelaide, South Australia, Australia

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Adelaide, South Australia, Australia

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Ashford, South Australia, Australia

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Woodville, South Australia, Australia

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Box Hill, Victoria, Australia

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Clayton, Victoria, Australia

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Clayton, Victoria, Australia

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East Melbourne, Victoria, Australia

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Fitzroy, Victoria, Australia

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Freemantle, Western Australia, Australia

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Nedlands, Western Australia, Australia

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Perth, Western Australia, Australia

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Melbourne, , Australia

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Graz, , Austria

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Innsbruck, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Antwerp, , Belgium

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Bruges, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Herestraat, , Belgium

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Yvoir, , Belgium

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Goiania - GO, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Hamilton, , Canada

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Brno, , Czechia

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Hradec Králové, , Czechia

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Prague, , Czechia

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Angers, , France

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Bordeaux, , France

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Le Mans, , France

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Lille, , France

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Limoges, , France

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Nantes, , France

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Nice, , France

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Pessac, , France

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Rennes, , France

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Rouen, , France

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Tours, , France

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Augsburg, , Germany

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Dessau, , Germany

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Frankfurt, , Germany

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Greifswald, , Germany

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Kiel, , Germany

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Würzburg, , Germany

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Athens, , Greece

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Heraklion, , Greece

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Ahmedabad, , India

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Bangalore, , India

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Delhi, , India

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Mumbai, , India

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Nashik, , India

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New Delhi, , India

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Pune, , India

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Trivandrum, , India

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Ashkelon, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Rehovo, , Israel

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Milan, , Italy

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Novara, , Italy

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Roma, , Italy

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Rome, , Italy

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Rozzano, , Italy

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Verona, , Italy

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Klaipėda, , Lithuania

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Hamilton, , New Zealand

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Palmerston North, , New Zealand

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Wellington, , New Zealand

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Bialystok, , Poland

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Gdansk, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Almada, , Portugal

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Braga, , Portugal

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Coimbra, , Portugal

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Lisbon, , Portugal

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Porto, , Portugal

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Viseu, , Portugal

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Brasov, , Romania

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Bucharest, , Romania

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Iași, , Romania

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Nizhny Novgorod, , Russia

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Obninsk, , Russia

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Ryazan, , Russia

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Saint Peterburg, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Yekaterinburg, , Russia

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Banská Bystrica, , Slovakia

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Bratislava, , Slovakia

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Martin, , Slovakia

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Madrid, , Spain

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Murcia, , Spain

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Palma de Mallorca, , Spain

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Salamanca, , Spain

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Toledo, , Spain

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Zaragoza, , Spain

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Bath, , United Kingdom

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Belfast, , United Kingdom

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Birmingham, , United Kingdom

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Bournemouth, , United Kingdom

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Edinburgh, , United Kingdom

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Glasgow, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Plymouth, , United Kingdom

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Surrey, , United Kingdom

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Taunton, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Canada Czechia France Germany Greece India Israel Italy Lithuania New Zealand Poland Portugal Romania Russia Slovakia Spain United Kingdom

References

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Byrd JC, Kipps TJ, Flinn IW, Castro J, Lin TS, Wierda W, Heerema N, Woodworth J, Hughes S, Tangri S, Harris S, Wynne D, Molina A, Leigh B, O'Brien S. Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Blood. 2010 Jan 21;115(3):489-95. doi: 10.1182/blood-2009-08-237727. Epub 2009 Oct 20.

Reference Type BACKGROUND
PMID: 19843887 (View on PubMed)

Pathan NI, Chu P, Hariharan K, Cheney C, Molina A, Byrd J. Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines. Blood. 2008 Feb 1;111(3):1594-602. doi: 10.1182/blood-2007-03-082024. Epub 2007 Nov 21.

Reference Type BACKGROUND
PMID: 18032710 (View on PubMed)

Byrd JC, O'Brien S, Flinn IW, Kipps TJ, Weiss M, Rai K, Lin TS, Woodworth J, Wynne D, Reid J, Molina A, Leigh B, Harris S. Phase 1 study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4448-55. doi: 10.1158/1078-0432.CCR-06-1463.

Reference Type BACKGROUND
PMID: 17671129 (View on PubMed)

Awan FT, Hillmen P, Hellmann A, Robak T, Hughes SG, Trone D, Shannon M, Flinn IW, Byrd JC; LUCID trial investigators. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2014 Nov;167(4):466-77. doi: 10.1111/bjh.13061. Epub 2014 Aug 8.

Reference Type DERIVED
PMID: 25130401 (View on PubMed)

Other Identifiers

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152CL201

Identifier Type: -

Identifier Source: org_study_id

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