Clinical trial NCT00391066: Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: CD23+/CD20+ B-cell CLL
CLL
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2006-10-23
Enrollment: 627
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete Response (CR) rate
timeFrame: Every 3 months until all patients have reached at least week 33
Secondary outcomes:
measure: Time to event variables (progression free survival, duration of response, time to next therapy, time to progression and overall survival)
timeFrame: Every 3 months until all patients have reached at least week 33
measure: Response variables
timeFrame: Every 3 months until all patients have reached at least week 33
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Alhambra
country: United States
facility: Research Site
state: California
city: Burbank
country: United States
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state: California
city: Fullerton
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state: California
city: La Jolla
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city: Long Beach
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city: Los Angeles
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city: Northridge
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city: Raleigh
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city: Gosford
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city: Waratah
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city: Westmead
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city: South Brisbane
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city: Adelaide
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city: Nedlands
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city: Melbourne
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country: Austria
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city: Antwerpen
country: Belgium
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city: Brugge
country: Belgium
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city: Bruxelles
country: Belgium
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city: Edegem
country: Belgium
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city: Yvoir
country: Belgium
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city: Goiania - GO
country: Brazil
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country: Germany
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country: Israel
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country: Israel
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country: Italy
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country: Italy
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country: Italy
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city: Verona
country: Italy
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city: Klaipeda
country: Lithuania
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city: Auckland
country: New Zealand
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city: Christchurch
country: New Zealand
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city: Hamilton
country: New Zealand
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city: Palmerston North
country: New Zealand
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city: Wellington
country: New Zealand
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city: Bialystok
country: Poland
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city: Gdansk
country: Poland
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city: Katowice
country: Poland
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city: Krakow
country: Poland
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city: Lodz
country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Almada
country: Portugal
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city: Braga
country: Portugal
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city: Coimbra
country: Portugal
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city: Lisbon
country: Portugal
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city: Porto
country: Portugal
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city: Viseu
country: Portugal
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city: Brasov
country: Romania
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city: Bucharest
country: Romania
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city: Iasi
country: Romania
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city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Samara
country: Russian Federation
facility: Research Site
city: Saratov
country: Russian Federation
facility: Research Site
city: St. Peterburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Banska Bystrica
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Madrid
country: Spain
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city: Murcia
country: Spain
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city: Palma de Mallorca
country: Spain
facility: Research Site
city: Salamanca
country: Spain
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city: Toledo
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Bath
country: United Kingdom
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Bournemouth
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Surrey
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
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. doi: 10.1182/blood-2007-03-082024. Epub 2007 Nov 21.
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. doi: 10.1158/1078-0432.CCR-06-1463.
citation: 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.