Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The overall goal of this clinical research study was to find out which of two different
      chemotherapy drug combinations, R-CHOP and R-HCVAD, is more effective in treating B-cell
      lymphoma.

      At this point, all participants will now be assigned to the R-HCVAD arm of the study.
      Researchers will study the safety and effectiveness of this drug combination.
    

Detailed description: 
      This study originally involved 2 different study drug regimens, R-CHOP and R-HCVAD. R-CHOP is
      made up of rituximab, cyclophosphamide, vincristine, and prednisone, and is the most common
      treatment for patients with non-Hodgkin's lymphoma. This combination was compared with
      R-HCVAD, which is made up of rituximab, doxorubicin, cyclophosphamide, vincristine, and
      dexamethasone.

      Rituximab (Rituxan®) is a humanized monoclonal antibody against cluster of differentiation
      antigen 20 (CD20) (a receptor in the surface of malignant B-cell lymphocytes). The drug has
      activity against aggressive and nonaggressive NHL of B-cell origin, and has been used in
      combination with chemotherapy. Cyclophosphamide is a type of drug know as an alkylating
      agent. Vincristine is a type of drug called vinca alkaloids. It is typically used in
      lymphomas, leukemias, and other tumors. Prednisone is a type of steroid. Dexamethasone is a
      steroid that may have activity against lymphomas. Methotrexate is an anti-cancer drug and a
      folic acid antagonist. It is used to treat solid tumors, lymphomas, leukemias, and autoimmune
      diseases.

      When this study began, participants were randomly assigned (as in the flip of a coin) to 1 of
      2 arms: Arm A (R-HCVAD alternating with a combination of rituximab, methotrexate, and Ara-C)
      or Arm B (R-CHOP). From this point on, all new participants will be treated with the Arm A
      combination, which has shown to be better.

      If you are found to be eligible to take part in this study, you will be given the study drugs
      in 21-day cycles. The cycles will alternate between R-HCVAD and a combination of rituximab,
      methotrexate, and Ara-C. During Cycle 1 (the R-HCVAD cycle), you will receive rituximab
      through a needle in your vein (intravenously, or "IV"), on Day 1. The infusion will take
      about 1 hour. Cyclophosphamide will be given by IV every 12 hours for 3 days. Each infusion
      of cyclophosphamide will take about 3 hours. Doxorubicin will be given as a 15-minute
      infusion on Day 5 with the supervision of a nurse. Your doctor may also choose to give you
      the doxorubicin over 24-48 hours using a small pump that you will carry around your waist in
      a "fanny pack." You will not have to stay in the hospital to receive this study drug.
      Vincristine will be given by IV, on Days 5 and 12. Each vincristine infusion will take about
      an hour. Dexamethasone will be given by mouth (as a pill, capsule, or tablet) on Days 2-5 and
      12-15. You will also be given other standard medications to help prevent possible side
      effects of these medications (such as nausea, vomiting, or rash).

      In Cycle 2 (the rituximab-methotrexate-Ara-C cycle), you will receive rituximab on Day 1. You
      will receive methotrexate by IV (after finishing the rituximab) on Days 2 and 3. The infusion
      will take about 24 hours. You will be given a small "fanny pack" with a pump inside that will
      slowly infuse the drug. You do not have to stay in the hospital while the drug is being
      given. You will be given Ara-C every 12 hours on Days 3-4 (a total of 4 doses). You will be
      given other standard medications to help prevent possible side effects of these medications
      (such as nausea, vomiting, or rash) during this cycle also.

      Leucovorin is given 12 hours after each methotrexate infusion. It is used to stop the action
      of the methotrexate and to prevent/lessen any side effects that the methotrexate may cause.

      During treatment, you will have blood draws (between 2-3 tablespoons) every week for routine
      tests. Every 4 weeks during treatment , you will be asked questions about your medical
      history and have a physical exam to check for any side effects. Every 2 cycles (about every 8
      weeks), you will have bone marrow biopsies performed (if they were positive before starting
      on this study), until they come back negative. You will have a positron emission tomography
      (PET) scan to see if the tumor is responding. Once the PET scan comes back negative, it will
      be up to your physician to decide if you need additional PET scan tests, and when. You will
      have CT scans of the chest, abdomen, pelvis, and neck every 2 cycles, if they were positive
      at the beginning of the study also. You may have additional testing done while on this study,
      if your physician feels that it is needed (for example, if it is needed to check for side
      effects).

      You may receive additional medication called "CNS prophylaxis" before receiving the study
      treatments. Your doctor will discuss these medications with you. The "CNS prophylaxis"
      consists of an alternating dose of either doxorubicin or methotrexate. The methotrexate will
      be given either by IV pump or by a "lumbar puncture" (a needle inserted into the space
      between the vertebrae in your back to infuse the drug directly into the spinal area). The
      doxorubicin will be given by IV. Changes in the dose level of CNS prophylaxis will be
      approved if you are at risk for or are experiencing serious side effects.

      You will receive the study drugs for up to 6-8 cycles on an outpatient basis. This means you
      will not have to be admitted to the hospital to receive the study drugs. You may be taken off
      study if the disease gets worse. If you experience intolerable side effects while taking any
      of the study drugs, your study doctor may decide to delay your treatment for up to 3 weeks
      (one study cycle) or to continue your therapy on the drugs at a lower dose. If the side
      effects become very severe, your doctor may decide to take you off of the study and stop the
      medication.

      At the end of your scheduled treatments, you will be asked to return to the clinic for
      follow-up visits every 6 months for the first, second, third, and fourth year after treatment
      on this study. You will then be followed every year after that. If your doctor feels it is
      necessary, you may have blood tests (about 3-5 teaspoons) performed at these visits. You will
      have bone marrow biopsies every other year for the first 2 years, if they were positive
      before you started on this study, and then every year after that. At these visits, you will
      be asked about any side effects you may have experienced and whether or not your cancer has
      come back. If your doctor feels there is a chance that the cancer has come back, he or she
      may schedule x-rays or scans in order to check. You will also be asked about any other
      therapies you may be having to treat your cancer, if it has come back.

      If you are taken off study for any reason, you will be asked to come back to the clinic for
      an end-of-treatment visit within 4 weeks from the last treatment. This visit will include a
      physical exam, routine blood tests (about 5-8 teaspoons), a blood-pregnancy test for women
      who are able to get pregnant, an ECG, and a chest x-ray.

      This is an investigational study. All of the study drugs are approved by the FDA for the
      treatment of lymphoma. Up to 66 patients will take part in this study. All of the patients
      will be enrolled at MD Anderson.
    

Intervention name(s): Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Dexamethasone; Methotrexate; Cytarabine; Prednisone
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Arm A: Rituximab 375 mg/m² by vein on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.; Arm A: Cyclophosphamide 300 mg/m^2 by vein (IVPB) over 3 hours every 12 hours x 6 doses on Days 2-4, Cycle 1 and alternating cycles.
Arm B: Cyclophosphamide 750 mg/m² by vein day 1; Arm A: Doxorubicin 50 mg/m^2/day by vein over 15 minutes (12 hours after last dose of cyclophosphamide) on Day 5, Cycle 1 and alternating cycles.; Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles.
Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle.; Arm A: Dexamethasone 40 mg by vein or by mouth daily x 4 on Days 2-5 and on days 12-15 of cycle 1 and alternating cycles.; Arm A: Methotrexate after finishing Rituximab, 200 mg/m2 by vein over 2 hours, then 800 mg/m2 by vein over 22 hours day 1 cycle 2.; Arm B: Cytarabine 3 g/m^2 by vein over 2 hours every 12 hours X 4 doses on days 3 & 4, cycle 2 and alternating cycles.; Arm B: Prednisone 100 mg by mouth (as a pill, capsule, or tablet) once a day on Days 1-5, each cycle.
Other intervention name(s): Rituxan; Cytoxan; Neosar; AD; Hydroxydaunomycin hydrochloride; Decadron; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride
Intervention MeSH terms: Cytarabine; Dexamethasone; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non-Hodgkin's Lymphoma; B-Cell Non-Hodgkin's Lymphoma; Lymphoma; Cyclophosphamide; Cytarabine; Doxorubicin; Hyper-CVAD; Methotrexate; Prednisone; Rituximab; Vincristine; R-CHOP; R-HCVAD; Dexamethasone; Decadron; Leucovorin; Ara-C; Cytosar; Cytoxan; DepoCyt; Cytosine arabinosine hydrochloride; AD; Hydroxydaunomycin hydrochloride; Neosar