Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)|
- 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.
- 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
- Toxicity Associated With This Regimen in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). [ Time Frame: From the date of registration to the to the date of last treatment evaluation, median number of days on treatment was 56 days. ]As per NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Version 3.0, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The number of participants experiencing grade 3 or higher toxicity will be reported here.
- Overall Survival [ Time Frame: 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. ]The Kaplan-Meier method will be used to estimate distributions in the B-CLL population.
- 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 ]
Progression is defined as one of the following:
- A ≥50% increase in the sum of the products of at least 2 lymph nodes on 2 consecutive determinations 2 weeks apart (at least one node must be ≥2 cm) or the appearance of new palpable lymph nodes, or
- A ≥50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin or the appearance of hepatomegaly or splenomegaly which was not previously present, or
- The transformation to a more aggressive histology (e.g. Richter's transformation), or
- A ≥ 50% increase in the absolute number of circulating lymphocytes.
The Kaplan-Meier method will be used to estimate time to progression.
|Study Start Date:||December 2005|
|Study Completion Date:||August 2010|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Experimental: Treatment (monoclonal antibody therapy)
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.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290810
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Tait Shanafelt||Mayo Clinic|