Phase II Trial of Alemtuzumab (Campath) and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in Relapsed or Refractory Diffuse Large B-Cell and Hodgkin Lymphomas
Condition: Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse
Intervention: Campath; Rituximab; EPOCH
Intervention description: campath plus etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and rituximab every 3 weeks for up to 6 cycles; rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and campath every 3 weeks for up to 6 cycles; Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) plus rituximab and campath every 3 weeks for up to 6 cycles
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Etoposide; Vincristine; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunosuppression; Microenvironment; Hodgkin Lymphoma; Microarray; B-Cell Lymphoma; Diffuse Large B-Cell Lymphoma

Summary:

      Background:

        -  Studies conducted at the National Cancer Institute suggest that certain chemotherapy
           drugs may be more effective if given by continuous infusion into the vein rather than by
           the standard method of rapid intravenous injection. One combination of six chemotherapy
           drugs, known as etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and
           rituximab (EPOCH-R), has had a high degree of effectiveness in people with certain kinds
           of cancer.

        -  Recent evidence also indicates that the effects of chemotherapy may be improved by
           combining the treatment with monoclonal antibodies, which are purified proteins that are
           specially made to attach to foreign substances such as cancer cells. A monoclonal
           antibody called campath (alemtuzumab) has been manufactured to attach to a protein
           called Campath-1 antigen (CD52) that may target tumor cells or the surrounding
           inflammatory cells.

        -  Researchers are interested in developing new treatments for large B-cell lymphoma or
           Hodgkin lymphoma that can best be treated with chemotherapy. This protocol is
           specifically for people with diffuse large B-cell or Hodgkin lymphomas that have not
           responded to standard treatments.

      Objectives:

      - To test whether giving campath (alemtuzumab) in combination with continuous infusion
      EPOCH-R chemotherapy will improve the outcome of lymphoma treatment.

      Eligibility:

      - Individuals 18 years of age and older who have large B-cell lymphoma or Hodgkin lymphoma
      that has not responded well to standard treatments.

      Design:

        -  During the study, patients will receive standard EPOCH-R chemotherapy, which includes
           the following drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,
           and rituximab. The additional drug, campath, will be given by intravenous (IV) infusion
           on the first day of treatment over several hours.

        -  When the campath IV infusion and rituximab IV infusion are complete, the drugs
           doxorubicin, etoposide, and vincristine will each be given by continuous IV infusion
           over the next 4 days (that is, continuously for a total of 96 hours). Cyclophosphamide
           will be given by IV infusion over several hours on Day 5. Prednisone will be given by
           mouth twice each day for 5 days.

        -  Patients may be given other drugs to treat the side effects of chemotherapy, to prevent
           possible infections, and to improve white blood cell counts.

        -  The campath-EPOCH-R therapy will be repeated every 21 days, as a cycle of therapy, for a
           total of 6 cycles. Following the fourth and sixth treatment cycles (approximately weeks
           12 and 18) of campath-EPOCH-R treatment, study researchers will perform blood tests and
           computed tomography (CT)/magnetic resonance imaging (MRI) scans on all patients to
           assess their response to the treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Previously treated or refractory classical large B-cell lymphomas, Grey-zone
                  lymphoma and Hodgkin lymphoma, including Lymphocyte predominant Hodgkin Lymphoma
                  (LPHL).

               2. Confirmed pathological diagnosis by the Laboratory of Pathology, National Cancer
                  Institute (NCI).

               3. Age greater than or equal to 18 years.

               4. Eastern Cooperative Oncology Group (ECOG) performance 0-2

               5. Laboratory tests: absolute neutrophil count (ANC) greater than or equal to
                  1000/mm(3), platelet greater than or equal to 75,000/mm(3). Creatinine less than
                  or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min;
                  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
                  equal to 5 times the upper limit of normal (ULN). Total bilirubin < 2.0 mg/dl
                  except < 5mg/dL in patients with Gilbert's (as defined as > 80% unconjugated
                  hyperbilirubinemia without other known cause); unless impairment due to organ
                  involvement by lymphoma.

        EXCLUSION CRITERIA:

          1. Active symptomatic ischemic heart disease, myocardial infarction or congestive heart
             failure within the past year. If echocardiogram (ECHO) is obtained, the left
             ventricular ejection fraction (LVEF) should exceed 40%.

          2. Human immunodeficiency virus (HIV) positive, because of the unknown effects of
             combined therapy with chemotherapy and an immunosuppressive agent on HIV progression.

          3. Female subject of child-bearing potential not willing to use an acceptable method of
             birth control (i.e. a hormonal contraceptive, intrauterine device, diaphragm with
             spermicide, condom with spermicide, or abstinence) for the duration of the study and
             two years beyond treatment completion.

          4. Female subject pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum beta-human chorionic gonadotrophin
             (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
             required for women without childbearing potential.

          5. Male subject unwilling to use an acceptable method for contraception for the duration
             of the study and one year beyond treatment completion.

          6. Invasive or active malignancy in past 2 years.

          7. Serious concomitant medical illnesses that would jeopardize the patient s ability to
             receive the regimen with reasonable safety.

          8. Active central nervous system (CNS) lymphoma. These patients have a poor prognosis and
             because they frequently develop progressive neurological dysfunction that would
             confound the evaluation of neurological and other adverse events.

          9. Systemic cytotoxic therapy within 3 weeks of treatment.