Clinical trial NCT00290810: Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
Official title: A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-02-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well bevacizumab works in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia. Monoclonal antibodies, such as 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. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer.

Detailed description: 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. Assess sensitivity to apoptosis/cell death of residual B-cell clone during therapy (e.g. is treatment selecting out a resistant clone).

II. Evaluate if the risk stratification parameters (ie immunoglobulin mutational, ZAP-70, FISH defects and /or CD38 status) corresponds to both baseline apoptosis/cell death and the rates of apoptosis of CLL B-cells when cultured with Bevacizumab.

III. Examine if Bevacizumab can be synergistic with other chemotherapeutic drugs such as chlorambucil or fludarabine.

IV. Assess if marrow vascularity is increased at entry to study and if it is modulated following therapy with Bevacizumab.

V. Examine the association of VEGF plasma levels at baseline with clinical responses to Bevacizumab.

VI. Examine the levels of VCAM at entry to the study and during treatment with Bevacizumab.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR).
timeFrame: Up to 5 years
Secondary outcomes:
measure: Toxicity Associated With This Regimen in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).
timeFrame: From the date of registration to the to the date of last treatment evaluation, median number of days on treatment was 56 days.
measure: Overall Survival
timeFrame: From the date of registration to the date of the event (i.e., death or the date of last follow-up), up to 5 years.
measure: Time to Progression
timeFrame: 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
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Tait Shanafelt
role: PRINCIPAL_INVESTIGATOR
References: