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

Chronic Lymphocytic Leukemia Clinical Trial

— LUCID  

Official title:

A Randomized, Open Label, Multicenter, Phase 2 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 Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00391066
• Other study ID #: 152CL201
• Status: Terminated
• Phase: Phase 2
• First received: October 19, 2006
• Last updated: September 17, 2015
• Start date: November 2006
• Est. completion date: December 2010

Study information

• Verified date: April 2011
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 627
• Est. completion date: December 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• FCR + Lumiliximab
Dose, schedule, and duration specified in the protocol
• FCR
Dose, schedule, and duration specified in protocol

Locations

Country	Name	City	State
Argentina	Research Site	Cordoba
Argentina	Research Site	Mendoza
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Ashford	South Australia
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Darlinghurst	New South Wales
Australia	Research Site	East Melbourne	Victoria
Australia	Research Site	Fitzroy	Victoria
Australia	Research Site	Freemantle	Western Australia
Australia	Research Site	Gosford	New South Wales
Australia	Research Site	Greenslopes	Queensland
Australia	Research Site	Herston	Queensland
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	Perth	Western Australia
Australia	Research Site	South Brisbane	Queensland
Australia	Research Site	St. Leonards	New South Wales
Australia	Research Site	Waratah	New South Wales
Australia	Research Site	Westmead	New South Wales
Australia	Research Site	Woodville	South Australia
Australia	Research Site	Woolloongabba	Queensland
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brugge
Belgium	Research Site	Bruxelles
Belgium	Research Site	Edegem
Belgium	Research Site	Ghent
Belgium	Research Site	Herestraat
Belgium	Research Site	Yvoir
Brazil	Research Site	Goiania - GO
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Paulo
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Hamilton
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec City
Canada	Research Site	Toronto	Ontario
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Prague
France	Research Site	Angers
France	Research Site	Bordeaux
France	Research Site	Le Mans
France	Research Site	Lille
France	Research Site	Limoges
France	Research Site	Nantes
France	Research Site	Nice
France	Research Site	Pessac
France	Research Site	Rennes
France	Research Site	Rouen
France	Research Site	Tours
Germany	Research Site	Augsburg
Germany	Research Site	Dessau
Germany	Research Site	Frankfurt
Germany	Research Site	Greifswald
Germany	Research Site	Kiel
Germany	Research Site	Wurzburg
Greece	Research Site	Athens
Greece	Research Site	Herakleion
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Delhi
India	Research Site	Mumbai
India	Research Site	Nashik
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Trivandrum
Israel	Research Site	Ashkelon
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Petach Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Rehovo
Italy	Research Site	Milano
Italy	Research Site	Novara
Italy	Research Site	Roma
Italy	Research Site	Rome
Italy	Research Site	Rozzano
Italy	Research Site	Verona
Lithuania	Research Site	Klaipeda
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Hamilton
New Zealand	Research Site	Palmerston North
New Zealand	Research Site	Wellington
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Lodz
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Portugal	Research Site	Almada
Portugal	Research Site	Braga
Portugal	Research Site	Coimbra
Portugal	Research Site	Lisbon
Portugal	Research Site	Porto
Portugal	Research Site	Viseu
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Iasi
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Samara
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	St. Peterburg
Russian Federation	Research Site	St. Petersburg
Slovakia	Research Site	Banska Bystrica
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Martin
Spain	Research Site	Madrid
Spain	Research Site	Murcia
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Salamanca
Spain	Research Site	Toledo
Spain	Research Site	Zaragoza
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Belfast
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Surrey
United Kingdom	Research Site	Taunton
United States	Research Site	Alhambra	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Austin	Texas
United States	Research Site	Bedford	Texas
United States	Research Site	Billings	Montana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Burbank	California
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbia	Missouri
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Fort Myers	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fredericksburg	Texas
United States	Research Site	Fullerton	California
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Houston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Kennewick	Washington
United States	Research Site	Kettering	Ohio
United States	Research Site	La Jolla	California
United States	Research Site	Long Beach	California
United States	Research Site	Los Angeles	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Maywood	Illinois
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Morristown	New Jersey
United States	Research Site	Nashville	Tennessee
United States	Research Site	Norfolk	Virginia
United States	Research Site	Northridge	California
United States	Research Site	Omaha	Nebraska
United States	Research Site	Overland Park	Kansas
United States	Research Site	Oxnard	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pomona	California
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Redondo Beach	California
United States	Research Site	Roanoke	Virginia
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Maria	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Spokane	Washington
United States	Research Site	St. Joseph	Michigan
United States	Research Site	St. Louis	Missouri
United States	Research Site	St. Louis	Washington
United States	Research Site	Yakima	Washington
United States	Research Site	Ypsilant,	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Greece,  India,  Israel,  Italy,  Lithuania,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  United Kingdom, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. Epub 2007 Nov 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) rate		Every 3 months until all patients have reached at least week 33	No
Secondary	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	No
Secondary	Response variables		Every 3 months until all patients have reached at least week 33	No