Clinical Trials /

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

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 IL-15 and mogamulizumab are safe and effective to treat people with 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 HIV, hepatitis B and C), urine, lung, and heart tests Bone marrow tests (if needed): A needle inserted in the participant s hip will take a small amount of marrow. CT, PET and/or MRI scans Tumor biopsy (if needed): A needle will take out a small piece of the participant s 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.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Mycosis Fungoides
  • Sezary Syndrome
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 200011
  • SECONDARY ID: 20-C-0011
  • NCT ID: NCT04185220

Conditions

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

Interventions

DrugSynonymsArms
rhIL-152- Experimental Treatment: Dose Expansion
Mogamulizumab2- Experimental Treatment: Dose Expansion

Purpose

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 IL-15 and mogamulizumab are safe and effective to treat people with 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 HIV, hepatitis B and C), urine, lung, and heart tests Bone marrow tests (if needed): A needle inserted in the participant s hip will take a small amount of marrow. CT, PET and/or MRI scans Tumor biopsy (if needed): A needle will take out a small piece of the participant s 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.

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 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 NK cells, monocytes and
           long- term CD8+ 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

        -  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 MTD of dose-escalated 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.
    

Trial Arms

NameTypeDescriptionInterventions
1- Experimental Treatment: Dose EscalationExperimentalIL-15 by 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 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.
  • rhIL-15
  • Mogamulizumab
2- Experimental Treatment: Dose ExpansionExperimentalIL-15 by CIV infusion at the MTD on days 1- 5 of each 28-day cycle (max 6 cycles) with mogamulizumab by 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.
  • rhIL-15
  • Mogamulizumab

Eligibility Criteria

        -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, NCI: mycosis fungoides/Sezary
             syndrome, or adult T-cell leukemia (chronic, acute, or lymphoma subtype by Shimoyama
             criteria)

          2. Patients with CD30+ 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 RECIL 2017 or 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

          6. ECOG performance status less than or equal to1 (Karnofsky greater than or equal to80%

          7. 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)

               -  AST(SGOT)/ALT(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

          8. 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.

          9. 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 3 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.

         10. Ability of subject or Legally Authorized Representative (LAR) 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, 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., CT scan
                  premedication)

          8. 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

          9. 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

         10. 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

         11. Patients with active bacterial infections, documented HIV infection or positive HIV
             1/2 antibodies at screening, PCR evidence for active or chronic hepatitis B or
             hepatitis C, or positive screening HBV/HCV serology without documentation of
             successful curative treatment

         12. 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

         13. 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

         14. 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

         15. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:28 days
Safety Issue:
Description:Frequency (number and percentage) of treatment emergent adverse events

Secondary Outcome Measures

Measure:Event free survival
Time Frame:every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Safety Issue:
Description:The response rate will be determined and reported along with a 95% confidence interval.
Measure:Progression-free survival
Time Frame:every 2 months for 6 months, every 3 months for 2 years, every 6 months for 2 years, then annually
Safety Issue:
Description:The response rate will be determined and reported along with a 95% confidence interval.
Measure:Overall response rate
Time Frame:6 cycles
Safety Issue:
Description:The response rate will be determined and reported along with a 95% confidence interval.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Antibody-Dependent Cell Cytotoxicity (ADCC)
  • CCR4
  • Monoclonal Antibodies

Last Updated

December 14, 2019