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NCT04185220

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

Completed Phase 1 Results posted Last updated 4 January 2023
What this trial tests

Phase 1 trial testing Recombinant human Interleukin-15 (rhIL-15) in Adult T-Cell Lymphoma/Leukemia in 6 participants. Completed in 18 May 2022.

Timeline
26 February 2020
Primary endpoint
6 November 2020
18 May 2022

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment6
Start date26 February 2020
Primary completion6 November 2020
Estimated completion18 May 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Adult T-Cell Lymphoma/Leukemia or Sezary Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15) Primary · 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.

GroupValue95% CI
All Participants2
Number of Grade 1-4 Treatment Related Adverse Events Primary · 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.

Grade 1 Alanine aminotransferase increased
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)2
Dose Level 2 (Interleukin-15 4mcg/kg/Day)1
Grade 1 Aspartate aminotransferase increased
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)2
Dose Level 2 (Interleukin-15 4mcg/kg/Day)1
Grade 1 Bronchial infection
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)1
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Grade 1 Chills
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)1
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Grade 1 Diarrhea
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)1
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Grade 1 Dysgeusia
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)2
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Grade 1 Fatigue
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)2
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Grade 1 Fever
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)9
Dose Level 2 (Interleukin-15 4mcg/kg/Day)1
Event Free Survival Secondary · 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.

GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)4.2± 1.46
Dose Level 2 (Interleukin-15 4mcg/kg/Day)2.1± 0.63
Progression-free Survival Secondary · 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.

GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)4.2± 1.46
Dose Level 2 (Interleukin-15 4mcg/kg/Day)2.1± 0.63
Number of Participants Overall Response Secondary · 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.

Complete Response
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Partial Response
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)1
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Relapsed Disease/Progressive Disease
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)2
Dose Level 2 (Interleukin-15 4mcg/kg/Day)3
Stable Disease
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Unconfirmed Complete Response
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · 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

GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)3
Dose Level 2 (Interleukin-15 4mcg/kg/Day)3
Number of Participants With a Dose-limiting Toxicity (DLT) Possibly, Probably or Definitely Related to Interleukin 15 (IL-15) or Mogamulizumab. Secondary · 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.

Possibly related to Interleukin 15
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Probably related to Interleukin 15
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Definitely related to Interleukin 15
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)2
Possibly related to mogamulizumab
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Probably related to mogamulizumab
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0
Definitely related to mogamulizumab
GroupValue95% CI
Dose Level 1 (Interleukin-15 2mcg/kg/Day)0
Dose Level 2 (Interleukin-15 4mcg/kg/Day)0

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level 1 (Interleukin-15 2mcg/kg/Day)
Serious: 3/3 (100%)
Deaths: 2/3
Dose Level 2 (Interleukin-15 4mcg/kg/Day)
Serious: 2/3 (67%)
Deaths: 1/3

Serious adverse events (15 terms)

ReactionSystemDose Level 1 (Interleukin-…Dose Level 2 (Interleukin-…
AcidosisMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
BacteremiaInfections and infestations
CPK increasedInvestigations
Capillary leak syndromeVascular disorders
Catheter related infectionInfections and infestations
Disease progressionGeneral disorders
Duodenal hemorrhageGastrointestinal disorders
FallInjury, poisoning and procedural complications
Hip fractureInjury, poisoning and procedural complications
HyponatremiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Multi organ failureGeneral disorders
MyositisMusculoskeletal and connective tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Other adverse events (61 terms — click to expand)

ReactionSystemDose Level 1 (Interleukin-…Dose Level 2 (Interleukin-…
FeverGeneral disorders
Aspartate aminotransferase increasedInvestigations
ChillsGeneral disorders
DysgeusiaNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
Neutrophil count decreasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Acute kidney injuryRenal and urinary disorders
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Blood lactate dehydrogenase increasedInvestigations
Bronchial infectionInfections and infestations
CPK increasedInvestigations
Capillary leak syndromeVascular disorders
Creatinine increasedInvestigations
DepressionPsychiatric disorders
DiarrheaGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
DysphagiaGastrointestinal disorders
Enterocolitis infectiousInfections and infestations
FallInjury, poisoning and procedural complications
FloatersEye disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
HematomaVascular disorders
HyperglycemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypertensionVascular disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypotensionVascular disorders
Infective myositisInfections and infestations
Mucositis oralGastrointestinal disorders
Nail infectionInfections and infestations
Nasal congestionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Acidosis, Acute kidney injury, Bacteremia, CPK increased, Capillary leak syndrome, Catheter related infection, Disease progression, Duodenal hemorrhage.

Data from ClinicalTrials.gov NCT04185220 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  2. IL-15 in the Combination Immunotherapy of Cancer.
    Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. · · 2020 · cited 187× · PMID 32508818 · DOI 10.3389/fimmu.2020.00868
  3. Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy.
    Yang Y, Lundqvist A. · · 2020 · cited 149× · PMID 33266177 · DOI 10.3390/cancers12123586
  4. Leukaemia: a model metastatic disease.
    Whiteley AE, Price TT, Cantelli G, Sipkins DA. · · 2021 · cited 139× · PMID 33953370 · DOI 10.1038/s41568-021-00355-z
  5. Interleukin 15 in Cell-Based Cancer Immunotherapy.
    Zhou Y, Husman T, Cen X, Tsao T, et al · · 2022 · cited 68× · PMID 35806311 · DOI 10.3390/ijms23137311
  6. Cytokine Based Immunotherapy for Cancer and Lymphoma: Biology, Challenges and Future Perspectives.
    Atallah-Yunes SA, Robertson MJ. · · 2022 · cited 43× · PMID 35529882 · DOI 10.3389/fimmu.2022.872010
  7. 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.
    Dubois SP, Miljkovic MD, Fleisher TA, Pittaluga S, et al · · 2021 · cited 35× · PMID 33883258 · DOI 10.1136/jitc-2020-002193
  8. Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies.
    Miljkovic MD, Dubois SP, Müller JR, Bryant B, et al · · 2023 · cited 17× · PMID 35475910 · DOI 10.1182/bloodadvances.2021006440

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