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)

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Brief Title

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)

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


      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.


      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.


      Adults 18 years and older with chronic or acute ATL who have not been helped by other


      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.

Detailed Description


        -  A previous trial alemtuzumab (CAMPATH-1) in patients with chronic, acute and
           lymphomatous subtype HTLV-1 associated ATL showed appreciable initial activity but no
           clear long-term impact.

        -  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 cluster of
           differentiation 8 (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, with improved survival compared to


      -To determine the safety, toxicity profile and the maximum tolerated dose (MTD) of s.c.
      rhIL-15 in combination with standard three times per week IV alemtuzumab treatment.


        -  Age greater than or equal to 18 years old

        -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1

        -  Diagnosis of adult T-cell leukemia (Human T-cell lymphotropic virus type 1 (HTLV-1)
           associated, chronic or acute), peripheral T-cell lymphoma (angioimmunoblastic,
           hepatosplenic, or not otherwise specified), cutaneous T-cell lymphoma (Stage III or IV,
           with leukemia involvement or erythrodemia), or T-cell prolymphocytic leukemia (T-PLL)

        -  Measurable or evaluable disease

        -  Adequate organ and bone marrow function as defined in the protocol.


        -  This is a single institution nonrandomized Phase I dose escalation study evaluating
           increasing doses of subcutaneous (SC) rhIL-15 in combination with alemtuzumab using a
           standard 3 + 3 dose escalation.

        -  Treatment will include s.c. rhIL015 daily Monday-Friday (M-F) weeks 1 and 2 (dose levels
           0.5- 2 mcg/kg/dose), followed by intravenous (IV) alemtuzumab beginning in week 3
           (escalating doses followed by standard dosing in weeks 4-6).

        -  Up to 30 patients will be enrolled in this study.

Study Phase

Phase 1

Study Type


Primary Outcome

Maximum Tolerated Dose (MTD) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15)

Secondary Outcome

 Number of Participants With a Clinical Response


T-Cell Lymphoma Relapsed


IL-15 plus

Study Arms / Comparison Groups

 1A-Interleukin 15 (IL-15) Followed by Alemtuzumab
Description:  IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks per dosing schema to determine the maximum tolerated dose (MTD)


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 19, 2017

Completion Date

June 15, 2021

Primary Completion Date

June 15, 2021

Eligibility 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

        -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.


          -  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

          -  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

          -  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

          -  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.




18 Years - N/A

Accepts Healthy Volunteers



Kevin Conlon, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party

Principal Investigator

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Kevin Conlon, M.D., Principal Investigator, National Cancer Institute (NCI)

Verification Date

April 2022