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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00391066




Registration number
NCT00391066
Ethics application status
Date submitted
19/10/2006
Date registered
23/10/2006
Date last updated
2/10/2015

Titles & IDs
Public title
Lumiliximab With Fludarabine, Cyclophosphamide, and Rituximab (FCR) Versus FCR Alone in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)
Scientific 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
Secondary ID [1] 0 0
152CL201
Universal Trial Number (UTN)
Trial acronym
LUCID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FCR + Lumiliximab
Treatment: Drugs - FCR

Active Comparator: 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

Experimental: 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


Treatment: Drugs: FCR + Lumiliximab
Dose, schedule, and duration specified in the protocol

Treatment: Drugs: FCR
Dose, schedule, and duration specified in protocol
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Response (CR) rate
Timepoint [1] 0 0
Every 3 months until all patients have reached at least week 33
Secondary outcome [1] 0 0
Time to event variables (progression free survival, duration of response, time to next therapy, time to progression and overall survival)
Timepoint [1] 0 0
Every 3 months until all patients have reached at least week 33
Secondary outcome [2] 0 0
Response variables
Timepoint [2] 0 0
Every 3 months until all patients have reached at least week 33

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2010
Sample size
Target
Accrual to date
Final
627
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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3128 - Box Hill
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3168 - Clayton
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3065 - Fitzroy
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- Freemantle
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- Perth
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- Melbourne
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Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT00391066
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00391066