- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00290810
Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
A Phase II Trial of Bevacizumab to Prevent or Delay Disease Progression in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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:
Complete Clinical Response: -CR without bone marrow biopsy confirmation. Nodular Partial Response: -CR with the presence of residual clonal nodules. Partial Response requires:
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Up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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From the date of registration to the to the date of last treatment evaluation, median number of days on treatment was 56 days.
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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.
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The Kaplan-Meier method will be used to estimate distributions in the B-CLL population.
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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.
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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
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Progression is defined as one of the following:
The Kaplan-Meier method will be used to estimate 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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tait Shanafelt, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, B-Cell
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibodies
- Immunoglobulins
- Bevacizumab
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
Other Study ID Numbers
- NCI-2009-00137 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (U.S. NIH Grant/Contract)
- N01CM62207 (U.S. NIH Grant/Contract)
- N01CM62205 (U.S. NIH Grant/Contract)
- 7211 (CTEP)
- MAYO-MC048C
- NCI-7211
- CDR0000459933
- MC048C (Other Identifier: Mayo Clinic)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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