Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas
Condition: T-Cell Peripheral Lymphoma; Gamma Delta Hepatosplenic T-Cell Lymphoma; Subcutaneous Panniculitis-Like T-Cell Lymphoma; NK T-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Panniculitis
Intervention: Rituximab; Etoposide; Siplizumab; Prednisone; Vincristine; Cyclophosphamide; Doxorubicin
Intervention description: Rituximab will be given with siplizumab and etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin every 21 days; Etoposide will be given with siplizumab and prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab every 21 days; Siplizumab will be given with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab every 21 days; Prednisone will be given with siplizumab and etoposide, vincristine, cyclophosphamide, doxorubicin and rituximab every 21 days; Vincristine will be given with siplizumab and etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab every 21 days; Cyclophosphamide will be given with siplizumab and etoposide, prednisone, vincristine, doxorubicin and rituximab every 21 days; Doxorubicin will be given with siplizumab and etoposide, prednisone, cyclophosphamide and rituximab every 21 days
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Etoposide; Vincristine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: CD2 Positive; Toxicity; EBV Lymphoma; Chemotherapy Naive; Maximum Tolerated Dose; Lymphoma; T-Cell Lymphoma; NK T-Cell Lymphoma

Summary:

      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 such combination of six chemotherapy
      drugs, known as Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, 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. This protocol is specifically for
      adults with the types of cancer known as T-cell and Naturel Killer (NK)-cell lymphomas, who
      have never received chemotherapy previously. The additional monoclonal antibody in the study,
      called siplizumab, has been manufactured to attach to the cluster of differentiation 2 (CD2)
      protein contained in these types of tumors.

      Study volunteers will need to undergo an initial period of evaluation that may take up to 3
      weeks and may be done on an outpatient basis. Evaluation may include some or all of the
      following tests: blood and urine tests, tests of lung and heart function, lumbar punctures to
      take samples of cerebrospinal fluid, magnetic resonance imaging (MRI) or computerized
      tomography (CT) scans, full-body positron emission tomography (PET) scans, bone marrow
      biopsies, and biopsies of suspected tumor areas.

      During the study, patients will receive EPOCH-R chemotherapy, which includes the following
      drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. The
      additional drug, siplizumab, will be given by IV infusion on the first day of treatment over
      several hours. When the siplizumab intravenous (IV) infusion is 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). When this infusion is completed,
      the drugs rituximab and 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 and to prevent possible infections.

      The siplizumab-EPOCH-R therapy will be repeated every 21 days, which is known as a cycle of
      therapy, for a total of 6 cycles. Following the fourth and sixth treatment cycles
      (approximately weeks 12 and 18) of siplizumab-EPOCH-R, study researchers will perform blood
      tests and CT/MRI scans on all patients to assess their response to the treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Cluster of differentiation 2 (CD2)-expressing lymphoid malignancy, confirmed by pathology
        or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, National
        Cancer Institute (NCI). At least 30% of the malignant cells must be CD2 positive for
        inclusion in this study.

        Patients with chemotherapy naive T & Natural Killer (NK) lymphomas, including but not
        limited to peripheral T cell lymphoma (nos), gamma-delta hepatosplenic T cell lymphoma,
        subcutaneous panniculitis-like T cell, NK-T cell lymphoma confirmed by pathology or flow
        cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. Patients with
        alk-positive anaplastic large cell lymphoma and patients with T-cell precursor disease are
        not eligible.

        Age greater than or equal to 18 years.

        Laboratory tests: Creatinine less than or equal to 1.5 mg/dL or creatinine clearance
        greater than or equal to 60 ml/min; bilirubin less than 2.0 mg/dl unless due to Gilbert's
        (unconjugated hyperbilirubinemia without other known cause), aspartate aminotransferase
        (AST) and alanine aminotransferase (ALT) less than or equal to 3 times upper limit of
        normal (ULN) (AST and ALT less than or equal to 6 times ULN for patients on
        hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation)
        and; Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3), platelet greater
        than or equal to 75,000/mm(3); unless impairment due to respective organ impairment by
        tumor.

        No active symptomatic ischemic heart disease, myocardial infarction or congestive heart
        failure within the past year.

        Patients must not have a marked baseline prolongation of Q wave, T wave (QT/QTc) interval
        (e.g., demonstration of a corrected QT interval (QTc) interval >500 milliseconds (ms)).

        Human immunodeficiency virus (HIV) negative, because of the unknown effects of combined
        therapy with chemotherapy and an immunosuppressive agent on HIV progression.

        Signed informed consent by the patient or patient's representative.

        Willing to use contraception.

        Not pregnant or nursing, because of the unknown effects of dose-adjusted etoposide,
        prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) or
        siplizumab on the developing fetus and infant.

        No serious underlying medical condition or infection that would contraindicate treatment.
        Patients with central nervous system (CNS) involvement are eligible for treatment on this
        study.

        EXCLUSION CRITERIA:

        Patients less than 18 years of age will be excluded because siplizumab has not been given
        to minors in combination with chemotherapy.