Lumiliximab in Combination With FCR in Subjects With Relapsed Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase I/II Study of Lumiliximab in Combination With Fludarabine, Cyclophosphamide, and Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103558
• Other study ID #: 152-30
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 10, 2005
• Last updated: September 17, 2015
• Start date: March 2004
• Est. completion date: March 2010

Study information

• Verified date: May 2010
• 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 an open label, Phase I/II, dose escalation research study of an investigational product called lumiliximab, given with FDA (Food and Drug Administration) approved products fludarabine, cyclophosphamide, and rituximab (FCR). The study duration is 17 visits over 42 months or until your disease progresses and you require additional CLL therapy. The total duration of participation in the study will be approximately 4 years, however your disease status will be followed indefinitely (forever).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age: 18 years and older

• Diagnosis of B-cell CLL by International Workshop on CLL (IWCLL) response criteria

• Relapsed CD23+ B-cell CLL

• Rai Stage III or IV, or Rai Stage I or II if determined to have disease progression as evidenced by rapid doubling or peripheral lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms

• Prestudy WHO Performance Status less than or equal to 2

• Signed, written Institutional Review Board (IRB)-approved informed consent

• Men & women of reproductive potential must agree to follow accepted birth control methods during treatment for 3 months after completion of treatment

• Acceptable liver function: Bilirubin less than or equal to 2.0 mg/dL (26 µmol/L), AST (SGOT) &/or ALT (SGPT) less than or equal to 2 times upper limit of normal

• Acceptable hematologic status: Platelet count less than or equal to 50 x 10^9/L, ANC less than or equal to 1 x 109/L

• Acceptable renal function: Serum creatinine less than or equal to 1.5 times upper limit of normal

Exclusion Criteria:

• Subjects who did not respond to prior FCR therapy (relapsed within 6 months of the last dose).

• Cancer 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

• Subjects who have had a prior allogenic bone marrow transplant (BMT) or autologous BMT or peripheral stem-cell transplant (PBSCT)

• Known infection with HIV, hepatitis B, or hepatitis C

• Uncontrolled diabetes mellitus

• Uncontrolled hypertension

• Transformation to aggressive B-cell malignancy (e.g., larger B-cell lymphoma, Richter's Syndrome, or prolymphocyte leukemia (PLL)

• Subjects with secondary malignancy requiring active treatment (except hormonal therapy)

• Subjects with medical conditions currently requiring long-term use (less than 1 month) of systemic corticosteroids

• Serious nonmalignant disease or laboratory abnormality, which, in the opinion of the investigator &/or sponsor, would compromise protocol objectives

• Active uncontrolled bacteria, 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 14 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

• Subjects with a history of fludarabine-induced autoimmune cytopenia

• Pregnant or currently breast-feeding

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Columbus	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

References & Publications (2)

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	Characterize the safety profile		monthly until month 12, then every 3 months for 24 months, then every 6 months until month 48	No
Secondary	Evaluate the pharmacokinetics of lumiliximab and rituximab		6 months	No