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.
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
Drug | Synonyms | Arms |
---|
rhIL-15 | | 1- Experimental Treatment: Dose Escalation |
Mogamulizumab | | 1- Experimental Treatment: Dose Escalation |
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
Name | Type | Description | Interventions |
---|
1- Experimental Treatment: Dose Escalation | Experimental | IL-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. | |
2- Experimental Treatment: Dose Expansion | Experimental | IL-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. | |
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 to 1 (Karnofsky greater than or equal to
80%
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 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.
10. 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., 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: | Active, not recruiting |
Lead Sponsor: | National Cancer Institute (NCI) |
Trial Keywords
- Antibody-Dependent Cell Cytotoxicity (ADCC)
- CCR4
- Monoclonal Antibody
Last Updated
August 19, 2021