EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma
Condition: Lymphoma, Mantle Cell; Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Rituximab (R); EPOCH; Bortezomib (B); Bortezomib; Bortezomib or observation
Intervention description: Rituximab is given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and bortezomib every 3 weeks for 6 cycles.; EPOCH is given with Rituximab and bortezomib every 3 weeks for 6 cycles.; Bortezomib is given alone for one cycle.; Bortezomib is given with EPOCH and rituximab every 6 weeks for 12 cycles.; At the beginning of Part C, patients are randomized to receive bortezomib maintenance or be observed w/o bortezomib.
Intervention MeSH terms: Rituximab; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Proteasome Inhibition; NF-Kappa-B; Gene Expression Signature; Cyclin D1; Translational Studies; Lymphoma; Mantle Cell Lymphoma; MCL

Summary:

      This study will evaluate the effectiveness of etoposide, prednisone, vincristine,
      cyclophosphamide, doxorubicin-rituximab (EPOCH-R) chemotherapy plus bortezomib for treating
      mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of
      the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug
      called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92
      percent had a complete remission of their disease after treatment with EPOCH-R. This study
      will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished
      will lengthen the time before the disease relapses and improve the overall cure rate.

      Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study.
      Candidates are screened with a medical history and physical examination, blood and urine
      tests, electrocardiogram, multi-gated acquisition scan (MUGA) or echocardiogram, imaging
      studies and biopsy to determine the extent of disease, and possible colonoscopy.

      Participants undergo treatment in three parts, as follows:

        -  Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug
           is injected into a vein over about 30 seconds.

        -  Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4
           weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week
           cycles, with all drugs administered over the first 5 days of each cycle. Patients take
           prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a
           96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered
           through a lightweight, portable infusion pump. Rituximab is given by vein over several
           hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given
           by vein over 30 seconds on day 1 before the rituximab and again on day 4.
           Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the
           chemotherapy infusion is completed. Patients are taught how to self inject granulocyte
           colony stimulating factor (G-CSF), a drug that helps boost white cell counts after
           chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of
           each cycle beginning day 6. Patients also take an antibiotic to help prevent infection
           during chemotherapy.

        -  Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly
           assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses
           over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue
           for up to 18 months or until the disease comes back or worsens. Patients who are
           assigned to the group that does not receive bortezomib will be offered the drug if their
           disease relapses.

      During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or
      other fluids to look at different genes and proteins that may be involved in the development
      of their lymphoma or the reaction of the immune system. A tissue biopsy is done before
      treatment begins and a day after treatment starts. Disease progress is followed with computed
      tomography (CT) scans and blood tests. When treatment is completed, patients whose cancer has
      disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease
      remains or recurs may be offered participation in another protocol if an appropriate one is
      available or are returned to the care of their local physician.

      ...
    

Eligibility criteria:

        -  ELIGIBILITY CRITERIA:

        Diagnosis of mantle cell lymphoma (confirmed at National Cancer Institute (NCI)). All
        variants are eligible.

        Age greater than or equal to 18 years.

        No prior treatment except for local radiation or a short course of steroids for control of
        symptoms.

        All stages of disease.

        Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3.

        Adequate major organ function (serum creatinine less than or equal to 1.5 mg/dl or
        creatinine clearance greater than 50 ml/min; bilirubin less than 2 mg/dl (total) except
        less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80%
        unconjugated; Absolute neutrophil count (ANC) greater than 1000 and platelets greater than
        75,000) unless impairment due to organ involvement by lymphoma.

        No myocardial infarction within 6 months prior to enrollment or New York Hospital
        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 electrocardiogram (ECG)
        abnormality at Screening has to be documented by the investigator as not medically
        relevant.

        No grade 2 greater than or equal to peripheral neuropathy within 14 days before enrollment.

        Ability to give informed consent.

        Human immunodeficiency virus (HIV) antibody negative.

        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. Female subject is not pregnant or breast-feeding. Confirmation that the subject is
        not pregnant must be established by a negative serum beta-human chorionic gonadotropin
        (beta-human chorionic gonadotropin (hCG)) pregnancy test result obtained during screening.
        Pregnancy testing is not required for post-menopausal or surgically sterilized women

        Male subject agrees to use an acceptable method for contraception for the duration of the
        study.

        No history of a prior invasive malignancy in past 5 years

        No known involvement of central nervous system by lymphoma

        No history of hypersensitivity to boron or mannitol.

        Patient has not received other investigational drugs with 14 days before enrollment.

        No serious medical or psychiatric illness likely to interfere with participation in this
        clinical study.

        Exclusion for fludeoxyglucose (FDG) scan is anyone exceeding the weight limit of the
        scanner (350 lb).