FCR and Bevacizumab in the Treatment of Relapsed CLL

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00448019
First received: March 13, 2007
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

The goal of this clinical research study is to learn if the combination of fludarabine, cyclophosphamide, rituximab, and bevacizumab is effective in treating chronic lymphocytic leukemia in patients who have already been treated with chemotherapy. The safety of this treatment will also be studied.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Rituximab
Drug: 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: Fludarabine, Cyclophosphamide, Rituximab and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression Free Survival (PFS) Rate [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: March 2007
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FCR + Bevacizumab
FCR = Fludarabine, Cyclophosphamide, Rituximab
Drug: Fludarabine
25 mg/m^2 IV over 30 minutes daily for 3 days
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Cyclophosphamide
250 mg/m^2 IV over 30 minutes daily for 3 days
Other Names:
  • Cytoxan
  • Neosar
Drug: Rituximab
375 mg/m^2 IV on Day 1 by prolonged infusion. All subsequent doses 500 mg/m^2 IV 30-minute infusion.
Other Name: Rituxan
Drug: Bevacizumab
10 mg/Kg IV on Day 3, course 1 over 30-90 minutes
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF

Detailed Description:

During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of treatment with the study drugs for 3-4 days and then about 3-1/2 weeks (25 days) of no treatment (about 4 weeks total). Treatment with the study drugs will be given for 4 days in a row on the first cycle, and 3 days in a row on Cycles 2-6. On Day 1 of each cycle, you will receive rituximab through a needle in a vein. On Cycle 1, since it is your first exposure to rituximab, it must be given slowly, so it may take 6-8 hours to complete. On the cycles after that, it can be given more rapidly, over 3-4 hours. Cyclophosphamide and fludarabine will be given separately through a needle in a vein on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2-6. Cyclophosphamide and fludarabine will each be given over 30 minutes. Bevacizumab will be given through a needle in a vein over 90 minutes on Day 3 of Cycle 1. If it is well tolerated, the next dose of Bevacizumab will be given over 60 minutes on Day 2 of Cycle 2. If the Cycle 2 dose is well tolerated, the next doses of Bevacizumab will be given over 30 minutes on Day 2 of Cycles 2-6. In addition to the study drugs, you may also be given fluids by vein to help flush the kidneys, to help prevent possible kidney damage. You may receive up to 6 cycles of treatment. Treatment will be given on an outpatient basis. The injections for each daily treatment visit should take less than 6 hours.

Up to 66 patients will take part in the study. All will be enrolled at M.D. Anderson.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of B-cell CLL
  • Relapsed, fludarabine-sensitive (duration of response > 6 months as assessed by prior treating physician) or fludarabine-naive patients
  • Rai Stage III or IV, or Rai Stage I or II if determined to have disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy, progressive splenomegaly, or B symptoms.
  • Prestudy WHO Performance Status </= 2.
  • Signed, written IRB-approved informed consent.
  • Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment.
  • Acceptable liver function: Bilirubin </= 2.0 mg/dL (26 umol/L), AST (SGOT) and/or ALT (SGPT) </= 2 times upper limit of normal.
  • Acceptable hematologic status: Platelet count >/= 50 x 10^9/L., ANC >/= 1 x 10^9/L.
  • Acceptable renal function: Serum creatinine </= 2.0 mg/dL

Exclusion Criteria:

  • Cancer radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or other investigational therapy within 4 weeks prior to Study Day 1.
  • Known infection with HIV, hepatitis B, or hepatitis C
  • Transformation to aggressive B-cell malignancy (e.g., large B-cell lymphoma, Richter's Syndrome, or prolymphocyte leukemia [PLL]).
  • Patients with secondary malignancy requiring active treatment (except hormonal therapy).
  • Active uncontrolled bacterial, viral, or fungal infections.
  • New York Heart Association Class II-IV cardiac disease or myocardial infarction within the past 6 months prior to Study Day 1.
  • Pregnant or currently breast-feeding.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study.
  • Blood pressure of > 150/100 mmHg
  • Unstable angina
  • History of stroke within 6 months
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study.
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1.
  • Urine protein:creatinine ratio >/= 1.0 at screening.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1.
  • Serious, non-healing wound, ulcer, or bone fracture.
  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: NCT00448019

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech
Investigators
Principal Investigator: Susan O'Brien, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00448019     History of Changes
Other Study ID Numbers: MDACC-2005-0992
Study First Received: March 13, 2007
Last Updated: December 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Fludarabine
Cyclophosphamide
Rituximab
Bevacizumab
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Cyclophosphamide
Fludarabine phosphate
Rituximab
Fludarabine
Bevacizumab
Vidarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 26, 2014