Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) and Alemtuzumab for People With Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL)
Condition: T-Cell Lymphoma Relapsed; Adult T-Cell Leukemia (ATL); Peripheral T-Cell Lymphoma (PTCL); Cutaneous T Cell Lymphoma (CTCL); T-Cell Prolymphocytic Leukemia
MeSH terms: Lymphoma; Leukemia; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, T-Cell, Cutaneous; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell
Intervention: IL-15 plus; alemtuzumab
Intervention description: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks.; Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
Intervention MeSH terms: Alemtuzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: T-cell Lymphoproliferative Disorder; CD4/CD25 Expressing T-cells in Blood and Lymphoid Tissues; Anti-CD52 Monoclonal Antibody; Antibody Dependent Cellular Cytotoxicity

Summary:

      Background:

      Adult T-cell leukemia (ATL) is a rare blood cancer. Researchers want to see if a combination
      of two drugs - recombinant human interleukin 15 (rhIL-15) and alemtuzumab - is a better
      treatment for ATL.

      Objectives:

      To test if giving rhIL-15 combined with alemtuzumab improves the outcome of therapy for ATL.
      Also, to determine the safe dose of this combination and identify side effects and effects on
      the immune system.

      Eligibility:

      Adults 18 years and older with chronic or acute ATL who have not been helped by other
      treatments.

      Design:

      Participants will be screened with tests that are mostly part of their usual cancer care.
      They will sign a separate consent form for this.

      Weeks 1 and 2: Participants will have a total of 10 visits. They will:

        -  Get rhIL-15 under the skin by needle.

        -  Have a physical exam and vital signs measured.

        -  Give blood samples.

        -  Answer questions about their health and their medicines.

      Week 3: Participants will stay in the clinic. They will:

        -  Get alemtuzumab infusions in a vein through a small catheter on days 1, 2, 3, and 5.

        -  Take medicines to decrease side effects.

        -  Have a computed tomography (CT) scan to evaluate the treatment.

        -  Have a physical exam and vital signs measured.

        -  Give blood samples.

      Answer questions about their health and medicines.

      Weeks 4, 5, and 6 will repeat week 3, without the CT scan. Some patients will just have
      outpatient visits these weeks.

      After treatment, participants will have follow-up visits every few months for up to 2 years.
      At these visits, participants will give blood samples and have CT scans.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Inclusion Criteria

          -  Age greater than or equal to 18 years; no upper age limit.

          -  Patients diagnosed with a leukemia or lymphoma as follows:

               -  Chronic or acute leukemia forms of Human T-cell lymphotropic virus type 1
                  (HTLV-1) associated adult T-cell leukemia;

               -  Peripheral T-cell lymphoma (angioimmunoblastic, hepatosplenic, or not otherwise
                  specified); or,

               -  Cutaneous T-cell lymphoma stage III or IV with circulating monoclonal cells (B1
                  or B2) and/or erythrodermia (T4)

               -  T-cell prolymphocytic leukemia (T-PLL)

        NOTE: Diagnosis must be validated by the Pathology Department, National Cancer Institute
        (NCI).

        -Patients must have measurable or evaluable disease.

        NOTE: All patients with greater than 10% abnormal cluster of differentiation 4 (CD4+)
        homogeneous cluster of differentiation 3 (CD3) low strongly cluster of differentiation 25
        (CD25+) expressing cells, or greater than 5% Szary cells/T-PLL, among the peripheral blood
        mononuclear cells (PBMCs) in the peripheral blood will be deemed to have evaluable disease.

          -  Abnormal T cells must be cluster of differentiation 52 (CD52+) as assessed by flow
             cytometry or immunohistochemistry.

          -  Patients must have a life expectancy of greater than or equal to 2 months.

          -  Patients must have been refractory or relapsed following front line therapy for Adult
             T-cell Leukemia (ATL); those with cutaneous T-cell lymphoma (CTCL) or peripheral
             T-cell lymphoma (PTCL) who have cluster of differentiation 30 (CD30+) disease must
             have progressed during or after treatment with brentuximab vedotin, or are unable to
             receive treatment due to allergy or intolerance.

          -  Patients must have recovered to less than grade 1 or to baseline from toxicity of
             prior chemotherapy or biologic therapy and must not have had major surgery,
             chemotherapy, radiation or biologic therapy within 2 weeks prior to beginning
             treatment. NOTE: Exceptions to this include events not considered to place the subject
             at unacceptable risk of participation in the opinion of the PI (e.g., alopecia).

          -  Carbon monoxide diffusing capacity alveolar volume (DLCO/VA) and forced expiratory
             volume (FEV) 1.0 > 50% of predicted on pulmonary function tests.

          -  Adequate laboratory parameters, as follows:

               -  Serum creatinine of less than or equal to 1.5 x the upper limit of normal

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the
                  upper limit of normal

          -  Absolute neutrophil count greater than or equal to 1,500/mm^3 and platelets greater
             than or equal to 100,000/mm^3.

          -  Eastern Cooperative Oncology Group (ECOG) less than or equal to 1.

          -  Patients must be able to understand and sign an Informed Consent Form.

          -  All patients must use adequate contraception during participation in this trial and
             for 4 months following completing therapy.

        EXCLUSION CRITERIA:

          -  Patients who have received any systemic corticosteroid therapy within 4 weeks prior to
             the start of therapy, or 12 weeks if given to treat graft versus host disease (GVHD),
             with the exception of physiological replacement doses of cortisone acetate or
             equivalent.

          -  Patients who have undergone allogeneic stem cell transplantation and have required
             systemic treatment for GVHD (including but not limited to oral or parenteral
             corticosteroids, ibrutinib, and extracorporeal phototherapy) within the last 12 weeks

          -  Clinical evidence of (parenchymal or meningeal) central nervous system (CNS)
             involvement or metastasis. In subjects suspected of having CNS disease, a magnetic
             resonance imaging (MRI) scan of the brain and lumbar puncture should be done to
             confirm.

          -  Documented human immunodeficiency virus (HIV), active bacterial infections, active or
             chronic hepatitis B, hepatitis C.

               -  Positive hepatitis B serology indicative of previous immunization (i.e.,
                  hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody
                  (HBcAb) negative) or a fully resolved acute hepatitis B infection is not an
                  exclusion criterion.

               -  If hepatitis C antibody test is positive, then the patient must be tested for the
                  presence of hepatitis C virus (HCV) by reverse transcription polymerase chain
                  reaction (RT-PCR) and be HCV ribonucleic acid (RNA) negative

        NOTE: HIV-positive patients are excluded from the study. Alemtuzumab may produce a
        different pattern of toxicities in patients with HIV infection; in addition, the depletion
        of T cells produced by alemtuzumab may have adverse effects on HIV-positive individuals.

          -  Concurrent anticancer therapy (including other investigational agents).

          -  History of severe asthma or presently on chronic inhaled corticosteroid medications
             (patients with a history of mild asthma not requiring corticosteroid therapy are
             eligible).

          -  Patients with smoldering and lymphomatous ATL.

          -  Pregnant or nursing patients.

          -  Patients who have previously received alemtuzumab are ineligible. NOTE: Patients with
             relapsed T-cell prolymphocytic leukemia (T-PLL) who have achieved at least a partial
             response to prior alemtuzumab are eligible.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, moderate/severe graft versus host disease, cognitive impairment, active
             substance abuse, or psychiatric illness/social situations that, in the view of the
             Investigator, would preclude safe treatment or the ability to give informed consent
             and limit compliance with study requirements.