Phase I Study of Recombinant Human IL-15 (rhIL-15) and Mogamulizumab for People With Refractory or Relapsed Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04185220
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 42.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Background:

Adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides/Sezary syndrome (MF/SS) are cancers that form in the T cells, a type of white blood cell that helps with the body's immune response. A combination of drugs might be able to better treat these cancers than existing therapies.

Objective:

To test if the drugs interleukin-15 (IL-15) and mogamulizumab are safe and effective to treat people with Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome (ATLL or MF/SS).

Eligibility:

People ages 18 and older with relapsed ATLL or MF/SS that has not responded to at least one standard treatment

Design:

Participants will be screened with:

Medical history

Physical exam

Blood (including human immunodeficiency virus (HIV), hepatitis B and C), urine, lung, and heart tests

Bone marrow tests (if needed): A needle inserted in the participants hip will take a small amount of marrow.

Computed tomography (CT), positron emission tomography (PET) and/or magnetic resonance imaging (MRI) scans

Tumor biopsy (if needed): A needle will take out a small piece of the participants tumor.

Participants will get the study drugs by vein for up to six 28-day cycles. They will get IL-15 the first 5 days of each cycle. They will get mogamulizumab on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of the other cycles. They will be hospitalized for 1 week in cycle

1. They may need to get a midline catheter. This is a soft tube put into a vein leading to the heart.

Participants will have repeats of the screening tests throughout the study.

After treatment, participants will have visits every 60 days for 6 months, every 90 days for 2 years, and then every 6 months for 2 years.

Condition or Disease	Intervention/Treatment	Phase
Adult T-Cell Lymphoma/Leukemia; Sezary Syndrome; Mycosis Fungoides	Drug: Recombinant human Interleukin-15 (rhIL-15); Biological: Mogamulizumab	Phase 1

Detailed Description

Background:

• Advanced mycosis fungoides, its leukemic form Sezary syndrome (MF/SS), and adult T- cell leukemia/lymphoma (ATLL) are all aggressive mature T-cell malignancies which are considered incurable without an allogeneic stem cell transplant.

• Mogamulizumab is a defucosylated monoclonal antibody directed towards C-C Motif Chemokine Receptor 4 (CCR4), a chemokine receptor expressed by the majority of MS/SS and ATLL cells. It is approved by the United States Food and Drug Administration for treatment of relapsed MF/SS and is recommended by the National Comprehensive Cancer Network for treatment of ATLL.

• Defucosylation of mogamulizumab is thought to enhance its capacity for antibody- dependent cell cytotoxicity (ADCC), which is mediated by natural killer (NK) cells and macrophages.

• The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of natural killer (NK) cells, monocytes and long- term cluster of differentiation 8 (CD) 8+ memory T-cells, has been assessed in several phase I trials in cancer patients.

• Concomitant administration of rhIL-15 with mogamulizumab may further enhance the ADCC capacity of the antibody and result in improved efficacy for patients with CCR4- expressing cancers.

Objectives:

-To determine the safety and toxicity profile and the maximum tolerated dose (MTD) of continuous intravenous infusion (civ) rhIL-15 administration in combination with standard intravenous (IV) mogamulizumab treatment

Eligibility:

• Age greater than or equal to 18 years of age

• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1

• Histologically or cytologically confirmed mycosis fungoides/S(SqrRoot)(Copyright)zary syndrome or adult T- cell leukemia/lymphoma relapsed after or refractory to at least one line of systemic treatment.

• Adequate organ and marrow function

Design:

• Open-label, single-center, non-randomized phase I study

• Standard "3 + 3" design will be used to determine the maximum tolerated dose (MTD) of dose-escalated recombinant human Interleukin-15 (rhIL-15) with fixed dose of mogamulizumab, with an expansion cohort at the MTD

• Maximum 6 cycles (28-day cycles) of combination therapy

• To explore all dose levels, including further evaluation in a dose expansion cohort, and to account for unevaluable patients the accrual ceiling will be set at 20 patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Study of Recombinant Human IL-15 (rhIL-15) and Mogamulizumab for Patients With Refractory or Relapsed Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome
• Actual Study Start Date: Feb 26, 2020
• Actual Primary Completion Date: Nov 6, 2020
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1- Experimental Treatment: Dose Escalation Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Drug: Recombinant human Interleukin-15 (rhIL-15); Interleukin 15 (IL-15) will be administered by continuous intravenous infusion in a dose-escalation 3 + 3 system with a starting dose of 2 mcg/kg/day and a second dose level of 4 mcg/kg/day on days 1-5 of each of six cycles.; Other Names: Human interleukin 15 ; Biological: Mogamulizumab; Mogamulizumab (intravenous (IV) over at least 1 hour) will be administered at a dose of 1 mg/kg on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle. Treatment will continue for a maximum of 6 cycles.; Other Names: Poteligeo
Experimental: 2- Experimental Treatment: Dose Expansion Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at the maximum tolerated dose (MTD) on days 1- 5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle.	Drug: Recombinant human Interleukin-15 (rhIL-15); Interleukin 15 (IL-15) will be administered by continuous intravenous infusion in a dose-escalation 3 + 3 system with a starting dose of 2 mcg/kg/day and a second dose level of 4 mcg/kg/day on days 1-5 of each of six cycles.; Other Names: Human interleukin 15 ; Biological: Mogamulizumab; Mogamulizumab (intravenous (IV) over at least 1 hour) will be administered at a dose of 1 mg/kg on days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle. Treatment will continue for a maximum of 6 cycles.; Other Names: Poteligeo

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15) [28 days]

   The MTD is the dose level at which no more than 1 of up to 6 patients experience DLT during the DLT evaluation window(s), or the dose below that at which at least 2 (of ≤6) patients have DLT. A dose-limiting toxicity (DLT) is defined as: any grade 3, 4, or 5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably or definitely related to IL-15 or mogamulizumab.

2. Number of Grade 1-4 Treatment Related Adverse Events [Date treatment consent signed to date off study, approximately 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.]

   Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

Secondary Outcome Measures

1. Event Free Survival [Up to one year]

   Event-free survival (EFS) is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first.

2. Progression-free Survival [Up to one year]

   Progression-free survival (PFS) is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first. Progressive Disease (PD) is new or increased lesions.

3. Number of Participants Overall Response [6 cycles (one cycle is 28 days)]

   Overall response was assessed by the Response Criteria for Adult T-cell Leukemia-Lymphoma. The response rate was determined and reported along with a 95% confidence interval. Complete Response (CR) is disappearance of all disease. Unconfirmed Complete Response (CRu) is stable residual mass in bulky lesion. Partial Response (PR) is regression of disease. Relapsed Disease (RD)/Progressive Disease (PD) is new or increased lesions. And Stable Disease (SD) is failure to attain CR/PR and no PD.

Other Outcome Measures

1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [Date treatment consent signed to date off study, approximately 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.]

   Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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.

2. Number of Participants With a Dose-limiting Toxicity (DLT) Possibly, Probably or Definitely Related to Interleukin 15 (IL-15) or Mogamulizumab. [First cycle of treatment (28 days)]

   A DLT is defined as any grade 3 (severe), 4 (life-threatening), or 5 (death related to adverse event) toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably or definitely related to IL-15 or mogamulizumab.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

-INCLUSION CRITERIA:

1. Patients must have one of the following histologically or cytologically proven relapsed and/or refractory to at least one line of systemic treatment, T-cell malignancies confirmed by the Laboratory of Pathology, National Cancer Institute (NCI): mycosis fungoides/Sezary syndrome, or adult T-cell leukemia (chronic, acute, or lymphoma subtype by Shimoyama criteria)

2. Patients with luster of differentiation 30 (CD30)+ Mycosis Fungoides/Sezary Syndrome (MF/SS) must have relapsed after or become intolerant to treatment with brentuximab vedotin

3. A formalin fixed tissue block or 15 slides of tumor sample (archival or fresh) must be available for performance of correlative studies. NOTE: Patients must be willing to have a tumor biopsy if prior tissue or adequate archival tissue is not available (i.e., post- enrollment and prior to treatment).

4. Disease must be measurable with at least one measurable lesion by Response Evaluation Criteria in Lymphoma (RECIL 2017) or modified severity-weighted assessment tool (mSWAT) criteria, or have an abnormal clonal T-cell population detectable by peripheral blood flow cytometry

5. Age >18 years

NOTE: Because no dosing or adverse event data are currently available on the use of rhIL-15 in combination with mogamulizumab in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

1. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 80%

2. Patients must have normal organ and marrow function as defined below:

• Absolute neutrophil count: greater than or equal to 1,000/mcL

• Platelets: > 100,000/mcL

• Total bilirubin: less than or equal to 1.5 X institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)Serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT)Serum glutamic pyruvic transaminase (SGPT): less than or equal to 2.5 X institutional ULN

• Serum creatinine: less than or equal to 1.5 X institutional ULN, OR Creatinine clearance: greater than or equal to 50 mL/min/1.73 m2 for patients with creatinine levels >1.5 institutional ULN

1. Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP)

NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.

1. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 6 months after completion of rhIL-15 and mogamulizumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

2. Ability of subject to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA:

1. Patients with other T-cell leukemias/lymphomas not specified in the inclusion criteria

2. Anti-cancer treatment within 2 weeks of the first dose of rhIL-15 and mogamulizumab (4 weeks for anti-cancer monoclonal antibody or investigational agents, 6 weeks for donor lymphocyte infusion,100 days for allogeneic stem cell transplant)

3. Systemic treatment for acute or chronic graft versus host disease (GVHD) within 12 weeks of the first dose of rhIL-15 and mogamulizumab

4. Cohort 1 (Dose Escalation) only: history of grade 3/4 GVHD, or active grade 1/2 GVHD regardless of treatment

5. Persisting toxicity related to prior therapy of grade > 1, with the exception of the following: alopecia, sensory neuropathy grade less than or equal to 2, or other grade less than or equal to 2 not constituting a safety risk based on investigator's judgment

6. Patients who are receiving any other investigational agents

7. Current use of immunosuppressive medication, EXCEPT for the following:

• Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)

• Systemic corticosteroids at physiologic doses less than or equal to 10 mg/day of prednisone or equivalent; or,

• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication)

1. Patients with previous malignant disease other than the target malignancy within the last 3 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ

2. Cohort 1 (Dose Escalation) only: Active or history of any autoimmune disease thought to be unrelated to their malignancy; for Cohort 2 (Dose Expansion), patients with history of autoimmune disease who are not on active immunosuppressive therapy

3. Patients with asthma requiring chronic inhaled or oral corticosteroids, or history of asthma requiring mechanical ventilation. Patients with a history of mild asthma that are on or can be switched to non-corticosteroid bronchodilator regimens are eligible

4. Patients with active bacterial infections, documented human immunodeficiency virus (HIV) infection or positive HIV 1/2 antibodies at screening, polymerase chain reaction (PCR) evidence for active or chronic hepatitis B or hepatitis C, or positive screening hepatitis B virus (HBV)/hepatitis C virus (HCV) serology without documentation of successful curative treatment

5. Presence of uncontrolled intercurrent illnesses including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that in the view of the Investigator would preclude safe treatment and limit compliance with study requirements

6. Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding. Because there is no significant preclinical information regarding the risks to a fetus or a newborn infant, all pregnant or breastfeeding woman will be excluded from participation in this trial

7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to rhIL-15 or mogamulizumab, unless felt to be in the best interests of the patient in the opinion of the investigator

8. Patients who received a live vaccine within 30 days of planned start of study therapy. Vaccination with a live vaccine while on trial is prohibited. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Contacts and Locations

Locations

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

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Milos Miljkovic, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 16, 2020
• Informed Consent Form - Nov 19, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: Kevin Conlon, MD, Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT04185220
• Other Study ID Numbers: 200011; 20-C-0011
• First Posted: Dec 4, 2019
• Last Update Posted: Dec 14, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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): Antibody-Dependent Cell Cytotoxicity (ADCC); CCR4; Monoclonal Antibody
• Additional relevant MeSH terms: Mycoses; Leukemia; Mycosis Fungoides; Sezary Syndrome; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Syndrome; Mogamulizumab

Study Results

Participant Flow

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Period Title: Dose Escalation
STARTED	3	3
COMPLETED	3	1
NOT COMPLETED	0	2
Period Title: Dose Escalation
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)	Total
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	3 100%	5 83.3%
>=65 years	1 33.3%	0 0%	1 16.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (8.73)	45.07 (14.04)	52.13 (13.01)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 16.7%
Male	2 66.7%	3 100%	5 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	3 100%	6 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 100%	2 66.7%	5 83.3%
White	0 0%	1 33.3%	1 16.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15)
Description	The MTD is the dose level at which no more than 1 of up to 6 patients experience DLT during the DLT evaluation window(s), or the dose below that at which at least 2 (of ≤6) patients have DLT. A dose-limiting toxicity (DLT) is defined as: any grade 3, 4, or 5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably or definitely related to IL-15 or mogamulizumab.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All participants that received Dose Level 1: Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 and Dose Level 2: Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	6
Number [mcg/kg/day]	2

2. Primary Outcome

Title	Number of Grade 1-4 Treatment Related Adverse Events
Description	Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. 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 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Grade 1 Alanine aminotransferase increased	2	1
Grade 1 Aspartate aminotransferase increased	2	1
Grade 1 Bronchial infection	1	0
Grade 1 Chills	1	0
Grade 1 Diarrhea	1	0
Grade 1 Dysgeusia	2	0
Grade 1 Fatigue	2	0
Grade 1 Fever	9	1
Grade 1 Hypomagnesemia	5	0
Grade 1 Neutrophil count decreased	1	1
Grade 1 Rash maculo-papular	3	0
Grade 2 Alanine aminotransferase	1	0
Grade 2 Anemia	9	0
Grade 2 Aspartate aminotransferase	2	0
Grade 2 Capillary leak syndrome	1	0
Grade 2 Bronchial infection	1	0
Grade 2 Chills	1	0
Grade 2 Creatine phosphokinase increased	1	0
Grade 2 Diarrhea	1	0
Grade 2 Dysgeusia	1	0
Grade 2 Fatigue	1	1
Grade 2 Fever	2	0
Grade 2 Infusion related reaction	1	1
Grade 2 Neutrophil count decreased	1	1
Grade 2 Rash maculo-papular	0	1
Grade 3 Alanine aminotransferase	1	0
Grade 3 Anemia	9	0
Grade 3 Creatine phosphokinase increased	2	0
Grade 3 Fall	0	1
Grade 3 Hip fracture	0	1
Grade 3 Hypoalbuminemia	2	0
Grade 3 Infusion related reaction	0	1
Grade 3 Rash maculo-papular	1	0
Grade 4 Acidosis	0	1
Grade 4 Capillary leak syndrome	0	1
Grade 4 Creatine phosphokinase increased	2	0
Grade 4 Acute kidney injury	0	1

3. Secondary Outcome

Title	Event Free Survival
Description	Event-free survival (EFS) is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first.
Time Frame	Up to one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Mean (Standard Error) [Months]	4.2 (1.46)	2.1 (0.63)

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first. Progressive Disease (PD) is new or increased lesions.
Time Frame	Up to one year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Mean (Standard Error) [Months]	4.2 (1.46)	2.1 (0.63)

5. Secondary Outcome

Title	Number of Participants Overall Response
Description	Overall response was assessed by the Response Criteria for Adult T-cell Leukemia-Lymphoma. The response rate was determined and reported along with a 95% confidence interval. Complete Response (CR) is disappearance of all disease. Unconfirmed Complete Response (CRu) is stable residual mass in bulky lesion. Partial Response (PR) is regression of disease. Relapsed Disease (RD)/Progressive Disease (PD) is new or increased lesions. And Stable Disease (SD) is failure to attain CR/PR and no PD.
Time Frame	6 cycles (one cycle is 28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Complete Response	0 0%	0 0%
Partial Response	1 33.3%	0 0%
Relapsed Disease/Progressive Disease	2 66.7%	3 100%
Stable Disease	0 0%	0 0%
Unconfirmed Complete Response	0 0%	0 0%

6. Other Pre-specified Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Description	Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Count of Participants [Participants]	3 100%	3 100%

7. Other Pre-specified Outcome

Title	Number of Participants With a Dose-limiting Toxicity (DLT) Possibly, Probably or Definitely Related to Interleukin 15 (IL-15) or Mogamulizumab.
Description	A DLT is defined as any grade 3 (severe), 4 (life-threatening), or 5 (death related to adverse event) toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably or definitely related to IL-15 or mogamulizumab.
Time Frame	First cycle of treatment (28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)	Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
Measure Participants	3	3
Possibly related to Interleukin 15	0 0%	0 0%
Probably related to Interleukin 15	0 0%	0 0%
Definitely related to Interleukin 15	0 0%	2 66.7%
Possibly related to mogamulizumab	0 0%	0 0%
Probably related to mogamulizumab	0 0%	0 0%
Definitely related to mogamulizumab	0 0%	0 0%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.
Arm/Group Title	Dose Level 1 (Interleukin-15 2mcg/kg/Day)		Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Arm/Group Description	Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 2 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.		Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kg days 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
All Cause Mortality
	Dose Level 1 (Interleukin-15 2mcg/kg/Day)		Dose Level 2 (Interleukin-15 4mcg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/3 (33.3%)
Serious Adverse Events
	Dose Level 1 (Interleukin-15 2mcg/kg/Day)		Dose Level 2 (Interleukin-15 4mcg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		2/3 (66.7%)
Gastrointestinal disorders
Duodenal hemorrhage	0/3 (0%)	0	1/3 (33.3%)	2
General disorders
Disease progression	1/3 (33.3%)	1	0/3 (0%)	0
Multi organ failure	0/3 (0%)	0	1/3 (33.3%)	1
Infections and infestations
Bacteremia	1/3 (33.3%)	1	0/3 (0%)	0
Catheter related infection	1/3 (33.3%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Fall	0/3 (0%)	0	1/3 (33.3%)	1
Hip fracture	0/3 (0%)	0	1/3 (33.3%)	1
Investigations
CPK increased	1/3 (33.3%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
Acidosis	0/3 (0%)	0	1/3 (33.3%)	1
Hyponatremia	0/3 (0%)	0	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Myositis	1/3 (33.3%)	1	0/3 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/3 (0%)	0	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/3 (33.3%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/3 (33.3%)	1	0/3 (0%)	0
Vascular disorders
Capillary leak syndrome	0/3 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Dose Level 1 (Interleukin-15 2mcg/kg/Day)		Dose Level 2 (Interleukin-15 4mcg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anemia	1/3 (33.3%)	18	1/3 (33.3%)	4
Cardiac disorders
Sinus tachycardia	1/3 (33.3%)	1	0/3 (0%)	0
Eye disorders
Floaters	1/3 (33.3%)	1	0/3 (0%)	0
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)	2	1/3 (33.3%)	1
Dysphagia	1/3 (33.3%)	1	0/3 (0%)	0
Mucositis oral	0/3 (0%)	0	1/3 (33.3%)	1
Oral pain	1/3 (33.3%)	1	0/3 (0%)	0
Vomiting	1/3 (33.3%)	1	0/3 (0%)	0
General disorders
Chills	2/3 (66.7%)	2	0/3 (0%)	0
Fatigue	2/3 (66.7%)	3	1/3 (33.3%)	1
Fever	3/3 (100%)	13	1/3 (33.3%)	1
Pain	1/3 (33.3%)	1	1/3 (33.3%)	1
Infections and infestations
Bronchial infection	1/3 (33.3%)	2	0/3 (0%)	0
Enterocolitis infectious	1/3 (33.3%)	1	1/3 (33.3%)	1
Infective myositis	1/3 (33.3%)	1	0/3 (0%)	0
Nail infection	0/3 (0%)	0	1/3 (33.3%)	1
Pharyngitis	1/3 (33.3%)	1	0/3 (0%)	0
Sinusitis	1/3 (33.3%)	1	0/3 (0%)	0
Thrush	1/3 (33.3%)	1	0/3 (0%)	0
Urinary tract infection	1/3 (33.3%)	1	0/3 (0%)	0
Wound infection	1/3 (33.3%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Fall	1/3 (33.3%)	1	0/3 (0%)	0
Infusion related reaction	1/3 (33.3%)	1	2/3 (66.7%)	2
Investigations
Alanine aminotransferase increased	1/3 (33.3%)	4	1/3 (33.3%)	1
Alkaline phosphatase increased	1/3 (33.3%)	2	0/3 (0%)	0
Aspartate aminotransferase increased	2/3 (66.7%)	4	1/3 (33.3%)	1
Blood lactate dehydrogenase increased	0/3 (0%)	0	1/3 (33.3%)	1
CPK increased	1/3 (33.3%)	4	0/3 (0%)	0
Creatinine increased	1/3 (33.3%)	1	1/3 (33.3%)	1
Neutrophil count decreased	2/3 (66.7%)	2	1/3 (33.3%)	2
Platelet count decreased	1/3 (33.3%)	1	1/3 (33.3%)	1
Serum amylase increased	1/3 (33.3%)	1	0/3 (0%)	0
Weight loss	1/3 (33.3%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
Anorexia	0/3 (0%)	0	1/3 (33.3%)	1
Hyperglycemia	1/3 (33.3%)	1	0/3 (0%)	0
Hyperkalemia	1/3 (33.3%)	1	0/3 (0%)	0
Hypoalbuminemia	1/3 (33.3%)	2	0/3 (0%)	0
Hypokalemia	1/3 (33.3%)	1	0/3 (0%)	0
Hypomagnesemia	1/3 (33.3%)	5	0/3 (0%)	0
Hyponatremia	0/3 (0%)	0	1/3 (33.3%)	2
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	1/3 (33.3%)	1	0/3 (0%)	0
Nervous system disorders
Dysgeusia	2/3 (66.7%)	3	0/3 (0%)	0
Psychiatric disorders
Depression	1/3 (33.3%)	1	0/3 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/3 (33.3%)	1	0/3 (0%)	0
Renal and urinary disorders - Other, Uric Acid increased	0/3 (0%)	0	1/3 (33.3%)	1
Urinary retention	1/3 (33.3%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/3 (66.7%)	2	0/3 (0%)	0
Nasal congestion	1/3 (33.3%)	2	0/3 (0%)	0
Oropharyngeal pain	1/3 (33.3%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Dry skin	1/3 (33.3%)	1	0/3 (0%)	0
Palmar-plantar erythrodysesthesia syndrome	1/3 (33.3%)	1	0/3 (0%)	0
Pruritus	1/3 (33.3%)	1	0/3 (0%)	0
Rash maculo-papular	2/3 (66.7%)	3	1/3 (33.3%)	1
Rash pustular	0/3 (0%)	0	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders - Other, Oral ulcer Right upper lip	1/3 (33.3%)	1	0/3 (0%)	0
Skin hyperpigmentation	1/3 (33.3%)	1	0/3 (0%)	0
Vascular disorders
Capillary leak syndrome	1/3 (33.3%)	1	0/3 (0%)	0
Hematoma	1/3 (33.3%)	1	0/3 (0%)	0
Hypertension	0/3 (0%)	0	1/3 (33.3%)	1
Hypotension	1/3 (33.3%)	1	0/3 (0%)	0
Thromboembolic event	0/3 (0%)	0	1/3 (33.3%)	1

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.