Evaluation of Safety and Efficacy of Fludarabine, Cyclophosphamide, and Rituximab (FCR) +/- Lumiliximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

• ClinicalTrials.gov Identifier: NCT00801060
• Recruitment Status: Terminated
• First Posted: December 3, 2008
• Last Update Posted: October 2, 2015
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: December 2, 2008
• First Posted Date: December 3, 2008
• Last Update Posted Date: October 2, 2015
• Study Start Date: February 2008
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2009)

• To evaluate the safety and tolerability of FCR+L compared with FCR alone in subjects with previously untreated CLL. [ Time Frame: June 2010 ]
• To evaluate the efficacy of FCR+L compared with FCR alone in subjects with previously untreated CLL. [ Time Frame: June 2010 ]

Original Primary Outcome Measures (submitted: December 2, 2008)

• To evaluate whether FCR+L versus FCR affects ECG results, with focus on the QTcF interval in subjects with previously untreated CLL. [ Time Frame: February 2010 ]
• To evaluate the effect of lumiliximab on the pharmacokinetics of fludarabine, cyclophosphamide, and rituximab in subjects with previously untreated CLL. [ Time Frame: February 2010 ]

• Change History: Complete list of historical versions of study NCT00801060 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: December 2, 2008)

• To evaluate the safety and tolerability of FCR+L compared with FCR alone in subjects with previously untreated CLL. [ Time Frame: February 2010 ]
• To evaluate the efficacy of FCR+L compared with FCR alone in subjects with previously untreated CLL. [ Time Frame: February 2010 ]
• To determine the pharmacokinetics of lumiliximab when given in combination with FCR in subjects with previously untreated CLL. [ Time Frame: February 2010 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Safety and Efficacy of Fludarabine, Cyclophosphamide, and Rituximab (FCR) +/- Lumiliximab in Subjects With Previously Untreated Chronic Lymphocytic Leukemia (CLL)
• Official Title: A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Fludarabine, Cyclophosphamide, and Rituximab (FCR) in Combination With Lumiliximab Versus FCR Alone in Subjects With Previously Untreated Chronic Lymphocytic Leukemia
• Brief Summary: This is a Phase 2, randomized, open-label, multicenter study in subjects with previously untreated CLL. It is designed to evaluate safety and efficacy of fludarabine, cyclophosphamide, rituximab (FCR) and lumiliximab versus FCR alone.
• Detailed Description: See protocol.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia

Intervention

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

Study Arms

• Experimental: Treatment Group A

  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

  Intervention: Drug: Lumiliximab + FCR
• Active Comparator: Treatment Group B

  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

  Intervention: Drug: FCR

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 8, 2009): 40
• Original Estimated Enrollment (submitted: December 2, 2008): 60
• Actual Study Completion Date: September 2010
• Actual Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

• Age 18 years or older.
• Previously untreated CD23+ and CD20+ B cell CLL.
• Life expectancy >6 months.
• Subjects with Rai Stage III or IV (Binet Stage C) or Rai Stage I or II (Binet Stage A or B) if determined to have active disease.
• World Health Organization (WHO) Performance Status ≤2.
• Normal ECG with QTc ≤450 msec for men and ≤460 msec for women. PR interval (Print) must be <240 msec and QRS complex <110 msec. T wave flattening and T wave inversion will be permitted.
• All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 12 months after their last dose of study treatment.
• Acceptable liver function at Screening.
• Acceptable hematologic status at Screening.
• Acceptable renal function at Screening.
• Subjects receiving any medication known to affect the QTc interval must discontinue the use of the medication or be on a stable dose of the medication for at least 3 months or 5 half-lives (whichever is longer) prior to Study Day 1, and continue (whenever possible) at the same dose throughout the study.

EXCLUSION CRITERIA:

• Any prior therapy for CLL.
• Known history or positive test result for human immunodeficiency virus.
• Known history of, or positive test result for Hepatitis C virus (test for Hepatitis C virus antibody) or Hepatitis B virus (test for Hepatitis B Surface Antigen and Hepatitis B Core Antibody) at Screening.
• Uncontrolled diabetes mellitus.
• Uncontrolled hypertension.
• Hypokalemia.
• Hypomagnesemia.
• New York Heart Association Class III or IV cardiac disease; myocardial infarction within the past 6 months prior to Study Day 1.
• Arrhythmia (other than sinus arrhythmia) within 30 days prior to Study Day 1.
• Evidence of active myocardial ischemia on ECG.
• Subjects with pacemakers.
• Transformation to aggressive B-cell malignancy.
• Secondary malignancy requiring active treatment.
• Any medical condition that would require long-term use (>1 month) of systemic corticosteroids during study treatment.
• Any serious nonmalignant disease or laboratory abnormality, which would confound the evaluation of adverse events (AEs).
• Active bacterial, viral, or fungal infections.
• Any known family history of long QT syndrome.
• 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.
• Presence of history of Coombs positive hemolytic anemia.
• Pregnant or currently breastfeeding at Screening.
• Prior exposure to lumiliximab or any other anti CD23 antibody.
• Subjects with known hypersensitivity to Chinese hamster ovary cell proteins, murine proteins, or any component of fludarabine, cyclophosphamide, rituximab, or the lumiliximab investigational treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, France, Poland, United Kingdom, United States

Administrative Information

• NCT Number: NCT00801060
• Other Study ID Numbers: 152CL202; EUDRACT NO: 2008-002204-25
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Biogen
• Study Sponsor: Biogen
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: April 2011