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Bevacizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00290810
First received: February 9, 2006
Last updated: April 21, 2014
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Biological: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 12
Study Start Date: December 2005
Study Completion Date: August 2010
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290810

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Tait Shanafelt Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00290810     History of Changes
Obsolete Identifiers: NCT01646996, NCT01664364
Other Study ID Numbers: NCI-2009-00137, NCI-2009-00137, MAYO-MC048C, NCI-7211, CDR0000459933, MC048C, 7211, P30CA015083, N01CM62205, N01CM62207
Study First Received: February 9, 2006
Results First Received: March 22, 2013
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Bevacizumab
Immunoglobulins
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014