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A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Phase 2
18 Years
Open (Enrolling)
B-cell Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia

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Trial Information

A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)


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


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

- 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:


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:


Principal Investigator

Tait Shanafelt

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




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



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