Clinical Trial: 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)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I Study Of Subcutaneous Recombinant Human IL-15 (S.C.rhIL-15) and Alemtuzumab for Patients With Refractory or Relapsed Chronic and Acute Adult T-Cell Leukemia (ATL

Brief 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

    Detailed Summary:

    Background:

    • A previously reported Lymphoid Malignancies Branch (LYMB) trial administering alemtuzumab (CAMPATH-1) to patients with chronic, acute and lymphomatous subtype HTLV-1 associated ATL showed appreciable initial activity but no clear long-term impact.

      • Overall response rate of 52% (n=15) in 29 patients.
      • Median duration of response 3.4 months.
      • Median overall survival 5.9 months.
    • Antibody dependent cellular cytotoxicity (ADCC) with polymorphonuclear neutrophils (PMNs), monocytes and natural killer (NK) cells acting as the effector cells is alemtuzumab s primary in vivo mechanism of action for depleting malignant leukemic or lymphomatous cells.
    • The immunologic effects of Interleukin-15 (IL-15), a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes and long-term CD8+ memory Tcells, has been assessed in several phase I trials in cancer patients.
    • Administration of recombinant human (rh) IL-15 as an intravenous bolus (IVB), continuous intravenous infusion (CIV) or subcutaneous injections (SC) into adult cancer patients has produced 5 to 50 fold expansion in the number of circulating NK cells at well tolerated doses in these patients.
    • Preclinical murine lymphoid malignancy models have shown efficacy from the administration of IL-15 and monoclonal antibodies.
    • In a syngeneic model, immunocompetent mice bearing an EL4 cell line transfected with human CD20 showed increased ADCC and improved survival for the mice treated with I
      Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome: Determine MTD and DLTs of s.c. rhIL-15 administered with 3 times per week IV Alemtuzumab [ Time Frame: after 6 weeks of IL-15 and alemtuzumab ]

      Original Primary Outcome: Same as current

      Current Secondary Outcome: Clinical response rate and progression free survival [ Time Frame: after 6 weeks of treatment ]

      Original Secondary Outcome:

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: February 20, 2016
      Date Started: January 28, 2016
      Date Completion: January 31, 2022
      Last Updated: May 20, 2017
      Last Verified: May 10, 2017