NCT00391066

Brief Summary

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.

Trial Health

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Trial Health Score

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

Strong global presence with extensive site network
Enrollment
627

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2006

Typical duration for phase_2

Geographic Reach
22 countries

172 active sites

Status
terminated

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

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 19, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 23, 2006

Completed
9 days until next milestone

Study Start

First participant enrolled

November 1, 2006

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
Last Updated

October 2, 2015

Status Verified

April 1, 2011

Enrollment Period

3.7 years

First QC Date

October 19, 2006

Last Update Submit

September 17, 2015

Conditions

Keywords

CD23+/CD20+ B-cell CLLCLL

Outcome Measures

Primary Outcomes (1)

  • Complete Response (CR) rate

    Every 3 months until all patients have reached at least week 33

Secondary Outcomes (2)

  • Time to event variables (progression free survival, duration of response, time to next therapy, time to progression and overall survival)

    Every 3 months until all patients have reached at least week 33

  • Response variables

    Every 3 months until all patients have reached at least week 33

Study Arms (2)

1

ACTIVE COMPARATOR

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

Drug: FCR

2

EXPERIMENTAL

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

Drug: FCR + Lumiliximab

Interventions

Dose, schedule, and duration specified in the protocol

2
FCRDRUG

Dose, schedule, and duration specified in protocol

1

Eligibility Criteria

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (194)

Research Site

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, 4120, 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, 5000, 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, 3128, Australia

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Clayton, Victoria, 3168, Australia

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Clayton, Victoria, Australia

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East Melbourne, Victoria, Australia

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Fitzroy, Victoria, 3065, 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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Québec, 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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Related Publications (4)

  • 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.

    PMID: 19843887BACKGROUND
  • 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.

    PMID: 18032710BACKGROUND
  • 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.

    PMID: 17671129BACKGROUND
  • 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.

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Receptors, Fclumiliximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Receptors, ImmunologicReceptors, Cell SurfaceMembrane ProteinsProteinsAmino Acids, Peptides, and Proteins

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 19, 2006

First Posted

October 23, 2006

Study Start

November 1, 2006

Primary Completion

July 1, 2010

Study Completion

December 1, 2010

Last Updated

October 2, 2015

Record last verified: 2011-04

Locations