Bevacizumab + CHOP-Rituximab in Untreated Mantle Cell Lymphoma
Condition: Untreated Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Bevacizumab; Rituximab; CHOP
Intervention description: 15 mg/kg on day 1 of each of 6 cycles; Rituximab will be administered prior to CHOP on day 3 of every cycle for a total of 6 cycles.
The dose to be administered is:
Rituximab: 375 mg/m2; Standard CHOP chemotherapy will be administered at full dose every 21 days for a total of 6 cycles. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 3 Doxorubicin: 50 mg/m2 IV on day 3 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 3 Prednisone: 100 mg PO days 3 - 7
Intervention MeSH terms: Bevacizumab; Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective

      1. To evaluate the safety profile of Bevacizumab (Bevacizumab™)- Rituximab (Rituxan®)-CHOP
      (RA-CHOP) in patients with newly diagnosed mantle cell lymphoma (MCL).

      Secondary Objectives

        1. To evaluate the response rate and time to disease progression of the RA-CHOP regimen in
           patients with newly diagnosed MCL.

        2. To prospectively characterize the angiogenic profiles of MCL patients during RA-CHOP
           treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with
             characteristic immunophenotypic profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+),
             CD23(-) and CD10(-)

          -  Patient has not received any prior anti-cancer therapy for lymphoma

          -  Laboratory parameters (unless considered by investigator to be due to lymphoma):

        Absolute neutrophil count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Hemoglobin > 7
        gm/dL Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN

          -  Patient has at least one tumor mass > 1.5 cm in one dimension

          -  Available tumor tissue for correlative studies (rebiopsy to be performed if needed)

          -  Patient is > 18 years old

          -  Patient has KPS > 50%

          -  Patient has signed IRB-approved informed consent

          -  Patient agrees to use birth control for duration of study

        Exclusion Criteria:

          -  Known central nervous system (CNS) involvement by lymphoma

          -  Known hepatitis infection

          -  Known HIV positivity

          -  Known history of renal disease with proteinuria; urine protein:creatinine ratio ³1.0
             at screening

          -  Uncontrolled hypertension: blood pressure of >150/100 mmHg at screening

          -  Unstable angina

          -  History of myocardial infarction within 6 months

          -  History of stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  Patient has ejection fraction < 50%

          -  Patient is taking coumadin, or has known history of thrombosis within last 6 months

          -  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

          -  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

          -  Concomitant malignancies or previous malignancies within the last five years, with the
             exception of adequately treated basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix.

          -  Patient is pregnant or nursing

          -  Patient is receiving other investigational drugs