A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
18 Years
N/A
Both
B-cell Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
Trial Information
A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
PRIMARY OBJECTIVES:
I. Assess the treatment success rate of Bevacizumab in patients with relapsed or refractory
B-cell chronic lymphocytic leukemia (CLL).
II. Assess the toxicity associated with this regimen in patients with relapsed or refractory
CLL
SECONDARY OBJECTIVES:
I. Overall Survival [Time Frame: From the date of registration to the date of the event
(i.e., death or disease progression) or the date of last follow-up, up to 5 years] II. Time
to Progression [Time Frame: From the date of registration to the date of the event (i.e.,
death or disease progression) or the date of last follow-up, up to 5 years] III. Duration of
Response Defined for All Evaluable Patients Who Have Achieved an Objective Response (i.e.,
CR, nPR, PR) [Time Frame: From the date at which the patient's objective status is first
noted to be a response to the date that progression or death is documented or to the date of
last follow-up, up to 5 years]
OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on
days 1 and 15.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 5 years.
Inclusion Criteria:
- Diagnosis of B-cell chronic lymphocytic leukemia (CLL)*, as defined by the following
phenotypic characteristics:
- Predominant population of cells share both B-cell antigens (CD19, CD20, or CD23)
as well as the T-cell antigen (CD-5), in the absence of other pan-T-cell markers
(CD-3, CD-2, etc.)
- Mantle cell lymphoma must be excluded by demonstrating the absence of the
t(11;14) by fluorescent in situ hybridization (FISH)
- Dim surface immunoglobulin expression
- Exclusively kappa and lambda light chains
- Peripheral blood absolute lymphocyte count > 5,000/mm^3
- Lymphocytosis must consist of small to moderate size lymphocytes, with ≤ 55%
prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
- Requires chemotherapy, as indicated by any of the following:
- Disease related symptoms, including the following:
- Weight loss ≥ 10% within the previous 6 months
- Extreme fatigue
- Fevers > 100.5°F for 2 weeks without evidence of infection
- Night sweats without evidence of infection
- Evidence of progressive marrow failure, as manifested by the development of or
worsening anemia (hemoglobin ≤ 10 g/dL) and/or thrombocytopenia (platelet count
≤ 100,000/mm^3)
- Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly
- Measurable and progressive lymphadenopathy
- Measurable (i.e., > 5,000/mm^3) and progressive lymphocytosis
- Progressive disease or relapsed after or refractory to 1 course of an alkylating
agent-based or purine nucleoside-based (e.g., fludarabine) regimen
- No marrow function attributable to dysplasia related to prior therapy
- ECOG performance status 0, 1, or 2
- Serum creatinine < 2 mg/dL
- If serum creatinine > 1.5 mg/dL but < 2 mg/dL, creatinine clearance must be ≥ 30
mL/min
- Platelet count > 30,000/mm^3
- Direct bilirubin ≤ 2 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other second malignancy within the past 2 years except squamous cell or basal cell
carcinoma of the skin or in situ carcinoma of the cervix
- No New York Heart Association class III or IV heart failure
- No blood pressure > 150/90 mm Hg
- No unstable angina
- No myocardial infarction or stroke within the past 6 months
- No clinically significant peripheral vascular disease
- No evidence of bleeding diathesis or coagulopathy
- No significant traumatic injury within the past 28 days
- Urine protein:creatinine (UPC) ratio ≤ 1.0
- Patients with a UPC ratio > 1.0 must undergo a 23-hour urine collection and must
demonstrate < 1 gram of protein per day
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months
- No serious, non-healing wound, ulcer, or bone fracture
- No active infections requiring oral or intravenous antibiotics
- No active bleeding or pathological conditions that carry a high risk of bleeding
(e.g., known varices)
- No thrombocytopenia requiring transfusion
- See Disease Characteristics
- More than 4 weeks since prior participation in an experimental drug study
- At least 8 weeks since prior rituximab
- At least 6 weeks since prior chemotherapy
- More than 28 days since prior major surgery or open biopsy
- More than 7 days since prior minor surgery, fine needle aspirations, or core biopsies
- No concurrent major surgery
- No concurrent participation in another experimental drug study
- Concurrent full-dose warfarin or low molecular weight heparin allowed provided
patient is on a stable dose AND INR is in range
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR).
Outcome Description:
The NCI Working Group criteria will be used to assess response to therapy. A confirmed response is defined as a response documented on 2 consecutive evaluations at least 4 weeks apart. Complete Response: No lymphadenopathy No hepatomegaly or splenomegaly Absense of constitutional symptoms Polymorphonuclear leukocytes ≥ 1500/ul Platelets > 100,000/ul Hemoglobin > 11.0 gm/dl Peripheral blood lymphocytes ≤ 4000/uL. Confirmation by Marrow Aspirate and biopsy. Complete Clinical Response: -CR without bone marrow biopsy confirmation. Nodular Partial Response: -CR with the presence of residual clonal nodules. Partial Response requires: ≥ 50% decrease in peripheral blood lymphocyte count ≥ 50% reduction in lymphadenopathy ≥ 50% reduction in size of liver and/or spleen 1 or more of the following: Polymorphonuclear leukocytes ≥ 1500/ul Platelets >100,000/ul Hemoglobin >11.0 gm/dl
Outcome Time Frame:
Up to 5 years
Safety Issue:
No
Principal Investigator
Tait Shanafelt
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00137
NCT ID:
NCT00290810
Start Date:
December 2005
Completion Date:
October 2013
Related Keywords:
- B-cell Chronic Lymphocytic Leukemia
- Refractory Chronic Lymphocytic Leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
