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

NCT04185220 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 20001120-C-0011
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult T-Cell Lymphoma/Leukemia; Sezary Syndrome; Mycosis Fungoides

Keywords

Antibody-Dependent Cell Cytotoxicity (ADCC); CCR4; Monoclonal Antibody

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15)

  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.

  28 days

• Number of Grade 1-4 Treatment Related Adverse Events

  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.

  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.

Secondary Outcomes (3)

• Event Free Survival

  Up to one year

• Progression-free Survival

  Up to one year

• Number of Participants Overall Response

  6 cycles (one cycle is 28 days)

Other Outcomes (2)

• 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.

• 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)

Study Arms (2)

1- Experimental Treatment: Dose Escalation

EXPERIMENTAL

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); Biological: Mogamulizumab

2- Experimental Treatment: Dose Expansion

EXPERIMENTAL

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); Biological: Mogamulizumab

Interventions

Recombinant human Interleukin-15 (rhIL-15) DRUG

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.

Also known as: Human interleukin 15

1- Experimental Treatment: Dose Escalation; 2- Experimental Treatment: Dose Expansion

Mogamulizumab BIOLOGICAL

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.

Also known as: Poteligeo

1- Experimental Treatment: Dose Escalation; 2- Experimental Treatment: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• Systemic treatment for acute or chronic graft versus host disease (GVHD) within 12 weeks of the first dose of rhIL-15 and mogamulizumab
• Cohort 1 (Dose Escalation) only: history of grade 3/4 GVHD, or active grade 1/2 GVHD regardless of treatment
• 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
• Patients who are receiving any other investigational agents
• 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)
• 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
• 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
• 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
• 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
• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Gordon MJ, Dubois S, Miljkovic MD, Ng S, Bryant B, Lakhotia R, Melani C, Pittaluga S, Conlon K, Waldmann T, Staudt LM, Wilson WH, Roschewski M. A phase 1 study of interleukin-15 in combination with mogamulizumab in relapsed and refractory T-cell malignancies. Blood Neoplasia. 2024 Nov 2;2(1):100054. doi: 10.1016/j.bneo.2024.100054. eCollection 2025 Feb.

  PMID: 40546724 DERIVED

• Dubois SP, Miljkovic MD, Fleisher TA, Pittaluga S, Hsu-Albert J, Bryant BR, Petrus MN, Perera LP, Muller JR, Shih JH, Waldmann TA, Conlon KC. Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies. J Immunother Cancer. 2021 Apr;9(4):e002193. doi: 10.1136/jitc-2020-002193.

  PMID: 33883258 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Sezary Syndrome; Mycosis Fungoides

Interventions

Interleukin-15; IL15RA protein, human; mogamulizumab

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Kevin Conlon
• Organization: National Cancer Institute

conlonkc@mail.nih.gov

240-858-3570

Study Officials

• Milos Miljkovic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2019
• First Posted: December 4, 2019
• Study Start: February 26, 2020
• Primary Completion: November 6, 2020
• Study Completion: May 18, 2022
• Last Updated: January 4, 2023
• Results First Posted: December 14, 2021

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)