Fludarabine Phosphate, Rituximab, and Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia That Has Relapsed or Not Responded To Treatment

NCT00845104 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2278.00NCI-2010-00316
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab and bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fludarabine phosphate together with rituximab and bevacizumab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving fludarabine phosphate together with rituximab and bevacizumab works in treating patients with B-cell chronic lymphocytic leukemia that has relapsed or not responded to treatment.

Conditions

B-cell Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  At 2 years

Secondary Outcomes (1)

• Response (complete, partial, or nodular partial response, progressive disease, stable disease, or minimal residual disease)

  At 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

Drug: fludarabine phosphate; Biological: rituximab; Biological: bevacizumab; Other: laboratory biomarker analysis; Other: flow cytometry; Genetic: polymerase chain reaction; Genetic: fluorescence in situ hybridization

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Arm I

rituximab BIOLOGICAL

Given IV

Also known as: C2B8 Monoclonal Antibody, IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm I

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, anti-VEGF rhuMAb, Avastin, rhuMAb VEGF

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

flow cytometry OTHER

Correlative studies

Arm I

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Arm I

fluorescence in situ hybridization GENETIC

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapse or refractory chronic Lymphocytic leukemia as defined by the WHO criteria and exhibit active disease requiring treatment as per the NCI working group in CLL
• Disease measurable defined by a combination of lymphocytosis \>= 5,000/mm\^3 in peripheral blood and lymphocytosis \>= 30% in bone marrow
• Confirmed CD20 expression on malignant CLL cells
• ECOG performance status of 0-2
• Life expectancy of at least 6 months
• Documented negative serologic testing for human immunodeficiency virus (HIV), hepatitis B (unless serologically positive due to prior vaccination), and hepatitis C within the year prior to enrollment
• Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
• Total serum bilirubin \< 2.5 x ULN
• Serum creatinine \< 1.5 x ULN
• Hemoglobin \> 8 g/dL
• Absolute neutrophil count (ANC) \> 1,000 cells/mm\^3
• Platelet count \> 50,000/mm\^3
• PT/INR and PTT \< 1.5 x ULN
• Within 2 weeks prior to registration, patients must have had a urinalysis negative for protein or a 24-hour urine collection demonstrating \< 500 mg protein
• If female and of child-bearing potential, have a negative serum pregnancy test within 14 days of enrollment

You may not qualify if:

• Patients must not require sustained support of hematopoietic cytokines or transfusion of blood products
• Presence of acute infection or other significant systemic illness
• Central nervous system involvement by malignancy, history of CVA, or seizure
• Previously received Bevacizumab
• Received transplant or Alemtuzumab within 3 months of enrollment
• Received an investigational agent, systemic corticosteroids, chemotherapy, immunotherapy, biologic therapy, antibody therapy (e.g., Rituximab) and/or radiation therapy within one month of enrollment
• Radiation to \> 25% of bone marrow or any radiation therapy within 4 weeks prior to start of therapy
• Inability to comply with study and/or follow-up procedures
• Life expectancy of less than 6 months
• Fludarabine-refractory disease (no response of disease to \>= 3 cycles of a fludarabine-based regimen or relapse within 6 months of fludarabine-based regimen)
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer (basal cell or squamous cell carcinoma), in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years unless approved by the PI
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure

Sponsors & Collaborators

• Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium: lead

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

fludarabine phosphate; Rituximab; Bevacizumab; Flow Cytometry; Polymerase Chain Reaction; In Situ Hybridization, Fluorescence

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Nucleic Acid Amplification Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Cytogenetic Analysis; Nucleic Acid Hybridization

Study Officials

• John Pagel

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 17, 2009
• First Posted: February 18, 2009
• Study Start: January 1, 2009
• Last Updated: March 6, 2015

Record last verified: 2015-03