FCR and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Fludarabine, Cyclophosphamide, Rituximab and Bevacizumab in the Treatment of Relapsed Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00448019
• Other study ID #: MDACC-2005-0992
• Secondary ID: NCI-2010-00591
• Status: Completed
• Phase: Phase 2
• First received: March 13, 2007
• Last updated: October 5, 2015
• Start date: February 2007
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Institutional Review Board (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., absolute neutrophil count (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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Fludarabine
25 mg/m^2 IV over 30 minutes daily for 3 days
• Cyclophosphamide
250 mg/m^2 IV over 30 minutes daily for 3 days
• Rituximab
375 mg/m^2 IV on Day 1 by prolonged infusion. All subsequent doses 500 mg/m^2 IV 30-minute infusion.
• Bevacizumab
10 mg/Kg IV on Day 3, course 1 over 30-90 minutes

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Jain P, Lee HJ, Qiao W, Wierda W, Benjamini O, Burger J, Ferrajoli A, Estrov Z, Kantarjian H, Keating M, O'Brien S. FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia. Cancer. 2014 Nov 15;120(22):3494-501. doi: 10.1002/cn — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Rate	Progression free survival (PFS) was defined as the time from the start of treatment to progression, which included treatment failure, relapse, or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	Baseline up to 5 years	No
Secondary	Number of Participants With Complete or Partial Response to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated Chronic Lymphocytic Leukemia (CLL)	Response criteria for Complete response (CR) - Nodes: None; Liver/Spleen Size: Not palpable; Symptoms: None; polymorphonuclear leukocytes (PMN): >1,500/µl; Platelets >100,000/µl; Hemoglobin (untransfused): >11,0 g/dl; Lymphocytes: <4,000/µl; Bone Marrow aspirate: <30% lymphocytes; Biopsy: No lymphocyte infiltrate; and for Partial Response (PR), Nodes: >/= 50% decrease; Liver/Spleen Size: >/= 50% decrease; Symptoms: None; Platelets >100,000/µl or > 50% improvement from baseline; Hemoglobin (untransfused): >11.0 g/dl or >50% improvement from baseline; Lymphocytes: >50% decrease; Biopsy: <30% lymphocytes with residual disease on biopsy for nodular PR (NPR).	Response assessed after three 4-week courses and after six courses, up to 24 weeks	No
Secondary	Overall Response Rate (ORR) to Fludarabine, Cyclophosphamide, Rituximab, and Bevacizumab Therapy in Previously Treated CLL	ORR defined as CR and PR response where response criteria for Complete response (CR) - Nodes: None; Liver/Spleen Size: Not palpable; Symptoms: None; polymorphonuclear leukocytes (PMN): >1,500/µl; Platelets >100,000/µl; Hemoglobin (untransfused): >11,0 g/dl; Lymphocytes: <4,000/µl; Bone Marrow aspirate: <30% lymphocytes; Biopsy: No lymphocyte infiltrate; and for Partial Response (PR), Nodes: >/= 50% decrease; Liver/Spleen Size: >/= 50% decrease; Symptoms: None; Platelets >100,000/µl or > 50% improvement from baseline; Hemoglobin (untransfused): >11.0 g/dl or >50% improvement from baseline; Lymphocytes: >50% decrease; Biopsy: <30% lymphocytes with residual disease on biopsy for nodular PR (NPR).	Response assessed after three 4-week courses and after six courses, up to 24 weeks	No

External Links

•   University of Texas MD Anderson Cancer Center Website