Study of Bortezomib in Combination With Cyclophosphamide and Rituximab
Condition: Mantle Cell Lymphoma; Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Bortezomib; Rituximab; Cyclophosphamide; Mesna; G-CSF
Intervention description: Bortezomib 1.3 mg/m^2 given intravenously over 3-5 seconds at the end of infusion of Rituximab on Day 1 of every cycle, then on Days 4, 8 and 11 of every cycle.; 375 mg/m^2 given intravenously over 6-8 hours on Day 1 of every 21-day study cycle.; 300 mg/m^2 intravenously over 3 hours 2 times each day (6 hours total each day) on Days 2, 3, and 4 of every cycle; 600 mg/m^2 intravenous continuous infusion (IVCI) over 24 hours daily for 3 days, 1 hour prior to Cyclophosphamide and complete by 12 hours after last dose of Cyclophosphamide.; 5 micrograms/kg subcutaneously daily starting 24-36 hours for 7 days after last dose of Bortezomib until granulocytes are more than 4 x 103/dl.
Intervention MeSH terms: Cyclophosphamide; Rituximab; Bortezomib; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Mantle Cell Lymphoma; Lymphoma; Bortezomib; Velcade; Rituximab; Rituxan; Cyclophosphamide; Cytoxan; Neosar; Mesna; Mesnex; G-CSF; Filgrastim; Neupogen

Summary:

      The goal of this clinical research study is to learn if bortezomib when given in combination
      with cyclophosphamide and rituximab can help to control mantle cell lymphoma. The safety of
      this drug combination will also continue to be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Confirmed diagnosis mantle cell lymphoma and its variants, excluding marginal zone and
             disease exclusively in the GI system. Patients should have measurable disease based on
             Cheson Criteria or Bone Marrow/tissue sample positive for mantle cell lymphoma. No
             prior therapy with a combination of bortezomib, cyclophosphamide and rituximab.

          2. Patients with performance status of 2 or less (Zubrod).

          3. Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma;
             absolute neutrophil count (ANC) >1000/mm^3 and platelets >100,000/mm^3 unless due to
             lymphoma.

          4. Cardiac ejection fraction 50% or greater.

          5. Ages 18 to 85.

          6. Patients must be willing to receive transfusions of blood products.

          7. Signed consent form.

          8. Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

          9. Female subject is either post-menopausal for at least 1 year before the screening
             visit, is surgically sterilized or if they are of childbearing potential, agree to
             practice 2 effective methods of contraception (i.e., a hormonal contraceptive,
             intra-uterine device, diaphragm with spermicide, condom with spermicide, or
             abstinence) from the time of signing the informed consent form through 30 days after
             the last dose of VELCADE, or agree to completely abstain from heterosexual
             intercourse.

         10. Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to
             1 of the following: practice effective barrier contraception during the entire study
             treatment period and through a minimum of 30 days after the last dose of study drug,
             or completely abstain from heterosexual intercourse.

        Exclusion Criteria:

          1. Human immunodeficiency virus (HIV) infection.

          2. Central nervous system (CNS) involvement.

          3. Patient has a platelet count of < 100 K (eg <30 x 10^9/L for studies with bortezomib
             alone) within 14 days before enrollment.

          4. Patient has an absolute neutrophil count of ANC (eg <1.0 x 10^9/L for studies with
             bortezomib alone)> within 14 days before enrollment.

          5. Patient has > 1.5 times Total Bilirubin

          6. Patient has a calculated or measured creatinine clearance of < 20 mL/minute creatinine
             clearance (eg <20 mL/minute for studies with bortezomib alone) > within 14 days before
             enrollment.

          7. Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.

          8. Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at Screening has to be documented by the investigator as not medically
             relevant.

          9. Patient has hypersensitivity to bortezomib, boron or mannitol.

         10. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum Beta-human chorionic gonadotropin
             (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
             required for post-menopausal or surgically sterilized women.

         11. Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days the start of this trial and throughout the duration of this
             trial.

         12. Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

         13. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
             require concurrent radiotherapy (which must be localized in its field size) should be
             deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
             date of therapy.

         14. Concurrent or previous malignancy whose prognosis is poor (< 90% probability of
             survival at 5 years).