Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma
Condition: Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: bortezomib; rituximab; cyclophosphamide; doxorubicin hydrochloride; vincristine; dexamethasone; filgrastim; pegfilgrastim; Autologous stem cell transplantation (ASCT)
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given SC; Given SC
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Bortezomib; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving rituximab together with combination
      chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma.
      Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some
      block the ability of cancer cells to grow and spread. Others find cancer cells and help kill
      them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as
      cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to stop
      the growth of cancer cells, either by killing the cells or stopping them from dividing.
      Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for
      cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill
      more cancer cells.

      Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C),
      vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically confirmed diagnosis of mantle cell lymphoma by
             demonstrating appropriate morphology plus at least one of the following on the biopsy
             specimen: nuclear cyclin D1+ by immunohistochemistry; t(11;14) by fluorescence in situ
             hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping

          -  No prior chemotherapy, immunotherapy or radiotherapy for mantle cell lymphoma; a brief
             course of steroids (< 14 days) for symptom relief or steroids for other indications
             are allowed

          -  Patients must have measurable disease; CT scans at baseline are required to define the
             extent of measurable disease; the scans must be obtained within 6 weeks prior to
             registration; combined CT/PET scans may be used for the baseline and subsequent
             evaluations if accurate tumor measurements can be obtained from the CT component

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count (ANC) > 1500 mm^3 (unless low count due to marrow
             involvement or splenomegaly)

          -  Platelets > 100,000 mm^3 (unless low counts due to marrow involvement or splenomegaly)

          -  Creatinine < 2 mg/dL

          -  Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to Gilbert's disease or due to
             liver involvement by lymphoma)

          -  Patients over the age of 45 must have a left ventricular ejection fraction (LVEF) of
             greater than 45% documented within 90 days prior to registration

          -  Patients must be tested for Hepatitis B surface antigen (HBs Ag) within 4 weeks prior
             to registration NOTE: HBs Ag positive patients are not excluded but will have more
             stringent monitoring of liver function tests

        Exclusion Criteria:

          -  Known HIV disease; an HIV test is not required for entry on study but is required if
             the patient is perceived to be at risk; patients with a history of intravenous drug
             use or any other behavior with an increased risk for HIV infection should be tested
             for exposure to the HIV virus; patients with known HIV are excluded since the
             immunocompromised state of patients with HIV infection or the concomitant use of
             highly active antiretroviral therapy (HAART) may result in more extensive dose
             modifications than intended for the intensive therapeutic regimen used in this study

          -  Pregnant or breast-feeding; all females of childbearing potential must have a blood
             test or urine study within 2 weeks prior to registration to rule out pregnancy; women
             of childbearing potential and sexually active males must use an accepted and effective
             method of contraception

          -  Grade 2 or higher baseline peripheral neuropathy

          -  Known hypersensitivity to boron or mannitol

          -  History of prior malignancy unless at least one of the following conditions are met:

               -  Malignancy was in-situ

               -  Malignancy was treated surgically or with local radiation therapy with curative
                  intent and the patient has been disease free for > 3 years

               -  Any adjuvant hormonal therapy must have been discontinued > 3 months prior to
                  registration

          -  Known central nervous system (CNS) involvement