A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- B-cell Chronic Lymphocytic Leukemia
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR).
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
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
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Number of Patients With Confirmed Objective Status of Complete Response (CR), Complete Clinical Response (CCR), Nodular Partial Response (nPR), or Partial Response (PR).
Time Frame: Up to 5 years
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
Secondary Outcomes
- Toxicity Associated With This Regimen in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).(From the date of registration to the to the date of last treatment evaluation, median number of days on treatment was 56 days.)
- Overall Survival(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.)
- Time to Progression(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)