Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Etoposide, carboplatin, ifosfamide; Rituximab, Ifosfamide, Etoposide, Carboplatin; Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine
Intervention description: Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.; It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.; It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights.
Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.
Intervention MeSH terms: Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Carmustine; Rituximab; Carboplatin; Etoposide; Etoposide phosphate; Mitoxantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Non-Hodgkin; Lymphoma; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; ifosfamide; etoposide; carboplatin; stem cell transplant; 08-026

Summary:

      About 60% of patients with DLBCL can be cured with a chemotherapy program. It is called
      RCHOP-21 (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). It is given
      once every 3 weeks, for 18 weeks. Each three weeks is a cycle. Some factors predict that you
      may not be cured with R-CHOP-21. The most common ones are:

        -  Stage - how much DLBCL, PMBL, or FL3B you have

        -  LDH - a blood chemistry marker; and

        -  Whether you can do your normal daily activities. (performance status) We think that the
           best way to cure more patients with poor risk factors is to add new treatment to R-CHOP.
           You will get different chemotherapy after 4 cycles. This type of treatment is called
           risk-adapted therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologic diagnosis of diffuse large B cell lymphoma, PMLBL, or follicular lymphoma
             grade 3B confirmed by the department of hematopathology at MSKCC: Patients with
             discordant bone marrow involvement (i.e. involvement by small cleaved cells or small
             lymphocytic lymphoma) are eligible.

          -  Tumors express CD20 as determined by immunohistochemistry.

             o Ki-67 evaluation of tumor tissue

          -  Patients must have stage III, or IV disease. Patients with IIX, disease must have at
             least one other age-adjusted IPI risk factor.

               -  KPS ≤ 70

               -  LDH > upper limit of normal

          -  All patients must have FDG-PET avid (minimum SUV 2.5) measurable disease

          -  Patients must have normal baseline cardiac function based upon echocardiogram or gated
             blood pool scan (MUGA) with an ejection fraction ≥ 50%

          -  Patients must have a serum creatinine of ≤ 1.5 mg/dl; if creatinine >1.5 mg/dl
             creatinine clearance must be >60 ml/minute.

          -  Patients must have ANC>1000/mcl and Platelets>50,000/mcl. If patient has cytopenias
             due to bone marrow involvement, these requirements are not applicable.

          -  Patients must have a bilirubin level of < 2.0 mg/dl in the absence of a history of
             Gilbert's disease (or pattern consistent with Gilbert's)

          -  Patients must be Hepatitis B surface antigen negative, Hepatitis B core antibody
             negative, and Hepatitis C negative.

          -  All patients of childbearing and child creating age must be using an acceptable form
             of birth control from the initiation of treatment on study until 1 year after
             completion of chemotherapy and/or transplant.

          -  Women who are pre-menopausal must have a negative pregnancy test

          -  Age between 18 and 65

          -  Patients must be HIV negative. This test may be pending in a patient without risk
             factors, as determined by the patient's physician.

          -  If patients have a history of malignancy other than cutaneous basal cell or squamous
             cell carcinoma, they must be disease-free for ≥ 5 years at the time of enrollment.

          -  Patients or their guardians must be capable of providing informed consent.

          -  Patients must be suitable to undergo stem cell transplant.

        Exclusion Criteria:

          -  Any lymphoma subtype other than DLBCL, PMLBL, follicular lymphoma grade 3B

          -  Patients with either parenchymal brain or lepto-meningeal involvement.

          -  No more than 14 days of prednisone therapy between the diagnostic biopsy of either
             DLBCL, PMLBL, or follicular lymphoma grade 3B and the initiation of treatment on
             study.

          -  Known pregnancy or breast-feeding

          -  Medical illness unrelated to NHL which in the opinion of the attending physician and
             principal investigator will preclude administration of chemotherapy safely. This
             includes patients with uncontrolled infection, chronic renal insufficiency, myocardial
             infarction within the past 6 months, unstable angina, cardiac arrhythmias other than
             chronic atrial fibrillation and chronic active or persistent hepatitis, or New York
             Heart Association Classification III or IV heart disease.

          -  History of any malignancy for which the disease-free interval is <5 years, excluding
             curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma
             in-situ of the cervix.