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
Intervention: Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Dexamethasone; Methotrexate; Cytarabine; Prednisone
Intervention description: 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.
Intervention MeSH terms: Cytarabine; Dexamethasone; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 16 Years
Maximum age: 60 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Confirmed diagnosis of previously untreated large B-cell Non Hodgkin's, Large Cell
             Lymphoma and B-Cell with high grade features. Other aggressive lymphomas such as
             Primary Mediastinal large B-cell Lymphomas will be also allowed to be included.

          2. Patients with performance status of 0-2 (Zubrod Scale).

          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 16 - 60 years (due to the fact that CHOP-R is not studied enough in younger
             patients and is not considered standard of care).

          6. Patients must be willing to receive transfusions of blood products.

          7. Age adjusted International Prognostic Index Score of 2 or more

          8. Previous steroids are allowed (if used to relieve some symptoms such as SVC, etc).

        Exclusion Criteria:

          1. Pregnancy (excluded due to the teratogenicity of the involved chemotherapy agents

          2. Positive HIV serology because of poor tolerance to this intense chemotherapy regimen

          3. Burkitt's lymphomas, and Mantle cell lymphoma, transformed follicular center cell
             lymphoma, follicular grade III.

          4. Any clinical or cytological diagnosis of central nervous system (CNS) involvement

          5. Any co-morbid medical, such as Child's Class C liver cirrhosis, end-stage renal
             disease, and symptomatic congestive heart failure, or psychiatric illnesses that
             preclude treatment with intense dose chemotherapy as determined by the primary
             investigator.

          6. Concurrent or previous malignancy whose prognosis is poor (< 90% probability of
             survival at 5 years)

          7. Active Hepatitis B or C. Chronic carriers for Hepatitis B will be excluded.