Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia
Condition: Waldenstrom's Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: Bortezomib; Rituximab; Valacyclovir
Intervention description: 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22.; 375 mg/m^2 IV on Day 8 and 22.; 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Intervention MeSH terms: Valacyclovir; Rituximab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Healthy volunteers: No
Keywords: Waldenstrom's Macroglobulinemia; Macroglobulinemic Lymphoma; Stem Cell Collection; Bortezomib; LDP-341; MLN341; PS-341; Velcade; Rituximab; Rituxan

Summary:

      The main goal of this clinical research study is to learn if Velcade ® (bortezomib) given
      with rituximab can help to control WM. This drug combination will allow researchers to
      collect your stem cells in case it is possible to transplant the stem cells as treatment if
      your WM gets worse. Researchers will also look at the safety and tolerability of this drug
      combination followed by treatment with other drug combinations.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with symptomatic macroglobulinemic lymphoma who have had no prior treatment,
             or whose prior treatment has been limited to steroids and/or alpha-interferon, are
             eligible. Macroglobulinemic lymphoma includes patients with either biopsy proven
             clonal lymphocytic or lymphoplasmacytic proliferation and monoclonal IgM. Also
             included are symptomatic patients with clonal proliferation producing a pathologic
             monoclonal IgM that causes cryoglobulinemia, peripheral neuropathy or cold agglutinin
             hemolytic anemia.

          2. Patients must have acceptable liver function (total bilirubin < 2.5mg/dL) and renal
             function (creatinine < 2.0mg/dL). Patients with impaired renal function will only be
             included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence
             Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass) that might
             reverse with improvement of disease.

          3. Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study.

          4. Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

          5. Patients must voluntarily sign an informed consent form indicating that they are aware
             of the investigational nature of the study, with the understanding that consent may be
             withdrawn by the subject at any time without prejudice to future care.

          6. Patient has a heart rate (HR) of greater than or equal to 50 bpm.

        Exclusion Criteria:

          1. Patient has a platelet count of <30x10^9/L within 28 days before enrollment unless due
             to >/= 75% marrow infiltration by macroglobulinemic lymphoma or splenomegaly.

          2. Patient has an absolute neutrophil count of <1.0x10^9/L within 28 days before
             enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma.

          3. Patient has a calculated or measured creatinine >/= to 2.0mg/dL on baseline
             evaluation. Patients with impaired renal function will only be included if the renal
             failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria,
             cryoglobulinemia, ureteral obstruction due to mass).

          4. Patient has >/= Grade 2 peripheral neuropathy on baseline evaluation.

          5. 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.

          6. Patient has hypersensitivity to boron, mannitol, or murine proteins.

          7. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum or urine Beta -human chorionic
             gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy
             testing is not required for post-menopausal or surgically sterilized women.

          8. Patient has received other investigational drugs within 14 days before enrollment

          9. Patient has a serious medical or psychiatric illness that is likely to interfere with
             participation in this clinical study.

         10. Eastern Cooperative Oncology Group (ECOG) performance status of > 2.

         11. Patient with a "currently active" second malignancy, other than non-melanoma skin
             cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not
             considered to have a "currently active" malignancy if they have completed therapy for
             a prior malignancy, are disease free from prior malignancies for > 5 years and are
             considered by their physician to be at less than 30 % risk of relapse.

         12. Patient with a lifetime cumulative dose of > 450 mg/m^2 of anthracyclines.

         13. Patients with an active hepatitis B infection.