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)

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT02689453
Collaborator
(none)
11
1
2
52.8
0.2

Study Details

Study Description

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 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.

Condition or Disease Intervention/Treatment Phase
  • Biological: IL-15 plus
  • Biological: alemtuzumab
Phase 1

Detailed Description

Background:
  • 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 controls.

Objective:

-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.

Eligibility:
  • 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.

Design:
  • 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 Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jan 19, 2017
Actual Primary Completion Date :
Jun 15, 2021
Actual Study Completion Date :
Jun 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1A-Interleukin 15 (IL-15) Followed by Alemtuzumab

IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks per dosing schema to determine the maximum tolerated dose (MTD)

Biological: IL-15 plus
Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks.
Other Names:
  • Interleukin-15
  • Biological: alemtuzumab
    Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Other Names:
  • Campath
  • Experimental: 1B - Interleukin-15 (IL-15) Followed by Alemtuzumab at the Maximum Tolerated Dose

    IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks at the maximum tolerated dose (MTD)

    Biological: IL-15 plus
    Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks.
    Other Names:
  • Interleukin-15
  • Biological: alemtuzumab
    Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Other Names:
  • Campath
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) [6 weeks]

      MTD is defined as the dose level at which no more than 1 of up to 6 participants experience a dose-limiting toxicity (DLT) during the first 6 weeks of treatment, and the dose below that at which at least 2 (of≤6) participants have DLT as a result of the drug. A DLT is defined as any grade 3 or 4 toxicity possibly, probably or definitely related to the rhIL-15 treatment that occurs during the first 6 weeks of treatment with some exceptions such as grade 3 or 4 lymphopenia, and grade 3 neutropenia for example.

    2. Number of Dose-limiting Toxicities (DLTs) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) Administered With 3 Times Per Week Intravenous (IV) Alemtuzumab [6 weeks]

      A DLT is defined as any grade 3 or 4 toxicity possibly, probably or definitely related to the rhIL-15 treatment that occurs during the first 6 weeks of treatment with some exceptions such as grade 3 or 4 lymphopenia, and grade 3 neutropenia for example.

    3. Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to Subcutaneous (s.c. rhIL-15) by Grade Who Have Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL)Cancer [Date treatment consent signed to date off study, approximately 16 months and 14 days for level 1, 18 months and 12 days for level 2, and 14 months and 24 days for level 3.]

      Here is the number of participants with serious adverse events possibly, probably, and/or definitely related to IL-15 (s.c. rhIL-15) by Grade assessed by the Common Terminology Criteria for Adverse Events (CTCAE 5.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

    Secondary Outcome Measures

    1. Number of Participants With a Clinical Response [At 3 weeks of treatment and again at 6 weeks of treatment]

      Clinical response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and reported along with a 95% confidence interval. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

    2. Progression Free Survival (PFS) [Restaging by computerized tomography (CT) occurred at the end of week 3 and week 6 during treatment, then every 60 days for 6 months, and every 90 days for up to 2 years after finishing treatment.]

      PFS was measured from the date of protocol consent until death or progressive disease occurs. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and reported along with a 95% confidence interval. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.

    3. Percentages of Circulating Lymphocytes (T and NK Cells) and the T-cell Subsets [At 6 weeks of treatment]

      Biological effects of rhIL-15 administered with alemtuzumab on the percentages of circulating lymphocytes (T and NK cells) and the T-cell subsets naïve, central and effector memory subsets (based on expression of cluster of differentiation 52 (CD52), neural cell adhesion molecule (CD56), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), memory T cells (CD45RO), memory T cells (CD45RA), cluster of differentiation 28 (CD28), apoptosis antigen 1 (CD95), C-C Chemokine Receptor 4 (CD194), C-C Motif Chemokine Receptor 7 (CCR7) and L-selectin (CD62L) using flow cytometry.

    4. Plasma Levels of Pro-inflammatory Cytokines [At 6 weeks of treatment]

      Plasma levels of pro-inflammatory cytokines using flow cytometry.

    Other Outcome Measures

    1. Number of Participants With Serious and/or Non-serious Adverse Events Regardless of Attribution Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [Date treatment consent signed to date off study, approximately 16 months and 14 days for level 1, 18 months and 12 days for level 2, and 14 months and 24 days for level 3.]

      Here is the number of participants with serious and/or non-serious adverse events regardless of attribution assessed by the Common Terminology Criteria for Adverse Events (CTCAE 5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • 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/mm3 and platelets greater than or equal to 100,000/mm3.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Kevin Conlon, MD, Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02689453
    Other Study ID Numbers:
    • 160062
    • 16-C-0062
    First Posted:
    Feb 24, 2016
    Last Update Posted:
    Apr 29, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kevin Conlon, MD, Principal Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail No participants were enrolled on Level 3 - 3 mcg/kg/dose of Interleukin 15 (IL-15) Followed by Alemtuzumab.
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group Description IL-15 for 10 doses over two weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Period Title: Overall Study
    STARTED 3 4 4
    COMPLETED 3 3 3
    NOT COMPLETED 0 1 1

    Baseline Characteristics

    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Total
    Arm/Group Description IL-15 for 10 doses over two weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. Total of all reporting groups
    Overall Participants 3 4 4 11
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    100%
    2
    50%
    4
    100%
    9
    81.8%
    >=65 years
    0
    0%
    2
    50%
    0
    0%
    2
    18.2%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    25.47
    (10.71)
    57.1
    (14.54)
    47.68
    (3.33)
    45.05
    (16.3)
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    1
    25%
    0
    0%
    2
    18.2%
    Male
    2
    66.7%
    3
    75%
    4
    100%
    9
    81.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    3
    100%
    4
    100%
    4
    100%
    11
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    100%
    3
    75%
    3
    75%
    9
    81.8%
    White
    0
    0%
    1
    25%
    1
    25%
    2
    18.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    4
    100%
    4
    100%
    11
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15)
    Description MTD is defined as the dose level at which no more than 1 of up to 6 participants experience a dose-limiting toxicity (DLT) during the first 6 weeks of treatment, and the dose below that at which at least 2 (of≤6) participants have DLT as a result of the drug. A DLT is defined as any grade 3 or 4 toxicity possibly, probably or definitely related to the rhIL-15 treatment that occurs during the first 6 weeks of treatment with some exceptions such as grade 3 or 4 lymphopenia, and grade 3 neutropenia for example.
    Time Frame 6 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Participants
    Arm/Group Description All participants who received at least one dose of subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) followed by Alemtuzumab
    Measure Participants 11
    Number [mcg/kg/dose]
    2
    2. Primary Outcome
    Title Number of Dose-limiting Toxicities (DLTs) of Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) Administered With 3 Times Per Week Intravenous (IV) Alemtuzumab
    Description A DLT is defined as any grade 3 or 4 toxicity possibly, probably or definitely related to the rhIL-15 treatment that occurs during the first 6 weeks of treatment with some exceptions such as grade 3 or 4 lymphopenia, and grade 3 neutropenia for example.
    Time Frame 6 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 3 4 4
    Possibly related
    1
    0
    0
    Probably related
    0
    0
    0
    Definitely related
    0
    0
    0
    3. Primary Outcome
    Title Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to Subcutaneous (s.c. rhIL-15) by Grade Who Have Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL)Cancer
    Description Here is the number of participants with serious adverse events possibly, probably, and/or definitely related to IL-15 (s.c. rhIL-15) by Grade assessed by the Common Terminology Criteria for Adverse Events (CTCAE 5.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
    Time Frame Date treatment consent signed to date off study, approximately 16 months and 14 days for level 1, 18 months and 12 days for level 2, and 14 months and 24 days for level 3.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group Description IL-15 for 10 doses over two weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 3 4 4
    Grade 3
    1
    33.3%
    1
    25%
    1
    25%
    Grade 4
    0
    0%
    0
    0%
    1
    25%
    Grade 5
    0
    0%
    0
    0%
    0
    0%
    4. Secondary Outcome
    Title Number of Participants With a Clinical Response
    Description Clinical response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and reported along with a 95% confidence interval. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
    Time Frame At 3 weeks of treatment and again at 6 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 3 4 4
    Complete Response
    1
    33.3%
    0
    0%
    1
    25%
    Partial Response
    0
    0%
    1
    25%
    1
    25%
    Stable Disease
    1
    33.3%
    1
    25%
    1
    25%
    Progressive Disease
    1
    33.3%
    2
    50%
    1
    25%
    5. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description PFS was measured from the date of protocol consent until death or progressive disease occurs. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and reported along with a 95% confidence interval. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.
    Time Frame Restaging by computerized tomography (CT) occurred at the end of week 3 and week 6 during treatment, then every 60 days for 6 months, and every 90 days for up to 2 years after finishing treatment.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 3 4 4
    Median (Full Range) [Days]
    78
    83
    138
    6. Secondary Outcome
    Title Percentages of Circulating Lymphocytes (T and NK Cells) and the T-cell Subsets
    Description Biological effects of rhIL-15 administered with alemtuzumab on the percentages of circulating lymphocytes (T and NK cells) and the T-cell subsets naïve, central and effector memory subsets (based on expression of cluster of differentiation 52 (CD52), neural cell adhesion molecule (CD56), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), memory T cells (CD45RO), memory T cells (CD45RA), cluster of differentiation 28 (CD28), apoptosis antigen 1 (CD95), C-C Chemokine Receptor 4 (CD194), C-C Motif Chemokine Receptor 7 (CCR7) and L-selectin (CD62L) using flow cytometry.
    Time Frame At 6 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    These analyses were not performed because there was pan lymphocyte depletion with the initiation of Campath (alemtuzumab) treatment and flow cytometry was not performed and there were not enough circulating lymphocytes to analyze.
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 0 0 0
    7. Secondary Outcome
    Title Plasma Levels of Pro-inflammatory Cytokines
    Description Plasma levels of pro-inflammatory cytokines using flow cytometry.
    Time Frame At 6 weeks of treatment

    Outcome Measure Data

    Analysis Population Description
    These analyses were not performed because there was pan lymphocyte depletion with the initiation of Campath (alemtuzumab) treatment and flow cytometry was not performed and there were not enough circulating lymphocytes to analyze.
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 0 0 0
    8. Other Pre-specified Outcome
    Title Number of Participants With Serious and/or Non-serious Adverse Events Regardless of Attribution Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
    Description Here is the number of participants with serious and/or non-serious adverse events regardless of attribution assessed by the Common Terminology Criteria for Adverse Events (CTCAE 5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date treatment consent signed to date off study, approximately 16 months and 14 days for level 1, 18 months and 12 days for level 2, and 14 months and 24 days for level 3.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group Description IL-15 for 10 doses over two weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    Measure Participants 3 4 4
    Count of Participants [Participants]
    3
    100%
    4
    100%
    4
    100%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 16 months and 14 days for level 1, 18 months and 12 days for level 2, and 14 months and 24 days for level 3.
    Adverse Event Reporting Description
    Arm/Group Title Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Arm/Group 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) IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment. IL-15 for 10 doses over two weeks followed by alemtuzumab for 4 weeks IL-15 plus: Recombinant Human IL-15 (subcutaneous (s.c.) rhIL-15) by s.c. injection Monday-Friday over two weeks. alemtuzumab: Alemtuzumab three times a week for a total of 4 weeks of alemtuzumab treatment.
    All Cause Mortality
    Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/4 (0%) 0/4 (0%)
    Serious Adverse Events
    Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 1/4 (25%) 1/4 (25%)
    Nervous system disorders
    Encephalopathy 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Psychiatric disorders
    Depression 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Vascular disorders
    Thromboembolic event 0/3 (0%) 0 1/4 (25%) 1 1/4 (25%) 1
    Other (Not Including Serious) Adverse Events
    Level 1 - 0.5 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab Level 2 - 1 mcg/kg/Dose of Interleukin-15 (IL-15) Followed by Alemtuzumab Level 3 - 2 mcg/kg/Dose of Interleukin 15 (IL-15) Followed by Alemtuzumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 4/4 (100%) 4/4 (100%)
    Blood and lymphatic system disorders
    Anemia 2/3 (66.7%) 9 1/4 (25%) 2 0/4 (0%) 0
    Cardiac disorders
    Sinus bradycardia 0/3 (0%) 0 1/4 (25%) 5 0/4 (0%) 0
    Sinus tachycardia 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 2
    Ear and labyrinth disorders
    Ear pain 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Eye disorders
    Blurred vision 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Gastrointestinal disorders
    Constipation 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Diarrhea 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Gastroesophageal reflux disease 0/3 (0%) 0 1/4 (25%) 2 0/4 (0%) 0
    Mucositis oral 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Nausea 1/3 (33.3%) 2 0/4 (0%) 0 1/4 (25%) 2
    Oral pain 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Vomiting 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 2
    General disorders
    Chills 1/3 (33.3%) 1 4/4 (100%) 7 2/4 (50%) 2
    Edema limbs 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Facial pain 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Fatigue 0/3 (0%) 0 2/4 (50%) 4 2/4 (50%) 3
    Fever 2/3 (66.7%) 3 3/4 (75%) 8 2/4 (50%) 4
    Flu like symptoms 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Injection site reaction 0/3 (0%) 0 0/4 (0%) 0 2/4 (50%) 4
    Localized edema 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Pain 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Hepatobiliary disorders
    Hepatic pain 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Infections and infestations
    Catheter related infection 1/3 (33.3%) 2 0/4 (0%) 0 0/4 (0%) 0
    Cytomegalovirus infection reactivation 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Herpes simplex reactivation 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Infections and infestations - Other, CMVpositive 1/3 (33.3%) 3 0/4 (0%) 0 0/4 (0%) 0
    Infections and infestations - Other, CMV viremia 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Shingles 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Sinusitis 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Skin infection 0/3 (0%) 0 1/4 (25%) 1 1/4 (25%) 1
    Upper respiratory infection 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Injury, poisoning and procedural complications
    Infusion related reaction 0/3 (0%) 0 3/4 (75%) 4 1/4 (25%) 3
    Investigations
    Alanine aminotransferase increased 2/3 (66.7%) 3 1/4 (25%) 1 0/4 (0%) 0
    Alkaline phosphatase increased 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Aspartate aminotransferase increased 2/3 (66.7%) 4 2/4 (50%) 2 0/4 (0%) 0
    Creatinine increased 0/3 (0%) 0 2/4 (50%) 3 0/4 (0%) 0
    Investigations - Other, CMV positive 1/3 (33.3%) 3 0/4 (0%) 0 0/4 (0%) 0
    Lymphocyte count decreased 2/3 (66.7%) 5 3/4 (75%) 7 1/4 (25%) 1
    Neutrophil count decreased 2/3 (66.7%) 4 2/4 (50%) 4 1/4 (25%) 1
    Platelet count decreased 1/3 (33.3%) 2 2/4 (50%) 2 0/4 (0%) 0
    Serum amylase increased 0/3 (0%) 0 1/4 (25%) 3 0/4 (0%) 0
    White blood cell decreased 2/3 (66.7%) 9 2/4 (50%) 3 0/4 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 0/3 (0%) 0 2/4 (50%) 2 0/4 (0%) 0
    Hypercalcemia 0/3 (0%) 0 2/4 (50%) 2 0/4 (0%) 0
    Hyperglycemia 1/3 (33.3%) 5 2/4 (50%) 3 0/4 (0%) 0
    Hyperkalemia 0/3 (0%) 0 1/4 (25%) 2 0/4 (0%) 0
    Hyperphosphatemia 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Hypoalbuminemia 0/3 (0%) 0 2/4 (50%) 3 0/4 (0%) 0
    Hypokalemia 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 1
    Hypomagnesemia 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Hyponatremia 0/3 (0%) 0 2/4 (50%) 8 0/4 (0%) 0
    Hypophosphatemia 2/3 (66.7%) 4 2/4 (50%) 2 1/4 (25%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Bone pain 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 2
    Musculoskeletal and connective tissue disorder - Other, tumor bleeding in left ankle 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Nervous system disorders
    Headache 0/3 (0%) 0 2/4 (50%) 2 1/4 (25%) 1
    Paresthesia 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Somnolence 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Psychiatric disorders
    Anxiety 0/3 (0%) 0 1/4 (25%) 1 1/4 (25%) 1
    Insomnia 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Skin and subcutaneous tissue disorders
    Nail changes 0/3 (0%) 0 1/4 (25%) 1 0/4 (0%) 0
    Pruritus 1/3 (33.3%) 1 0/4 (0%) 0 0/4 (0%) 0
    Rash maculo-papular 1/3 (33.3%) 1 3/4 (75%) 4 0/4 (0%) 0
    Urticaria 1/3 (33.3%) 1 0/4 (0%) 0 2/4 (50%) 5
    Vascular disorders
    Hypertension 0/3 (0%) 0 0/4 (0%) 0 1/4 (25%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Kevin Conlon
    Organization National Cancer Institute
    Phone 240-858-3570
    Email conlonkc@mail.nih.gov
    Responsible Party:
    Kevin Conlon, MD, Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT02689453
    Other Study ID Numbers:
    • 160062
    • 16-C-0062
    First Posted:
    Feb 24, 2016
    Last Update Posted:
    Apr 29, 2022
    Last Verified:
    Apr 1, 2022