This phase I trial studies the side effects and best dose of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570 in treating patients with peripheral T-cell lymphoma follicular variant or angioimmunoblastic T-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as anti-ICOS monoclonal antibody MEDI-570, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVE: I. To determine the safety, maximum tolerated dose and recommended phase II dose (RP2D) of anti-ICOS monoclonal antibody MEDI-570 (MEDI-570) in patients with refractory/relapsed peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), follicular lymphoma, mycosis fungoides (MF) and cutaneous T-cell lymphomas (CTCL). SECONDARY OBJECTIVES: I. To evaluate the pharmacokinetic profile of MEDI-570. II. To evaluate the overall response rate (ORR) and progression free survival (PFS) of MEDI-570 at all dose levels and in a 10-patient expansion cohort at the maximum tolerated dose (MTD). III. To determine short and long term effects of MEDI-570 at all dose levels on the immune system and on T-cell lymphocyte subsets. IV. To determine the relationship between ICOS expression on tumor cells and response to MEDI-570. EXPLORATORY OBJECTIVE: I. To evaluate biomarkers of response and resistance to MEDI-570 in the study population. OUTLINE: This is a dose-escalation study. Patients receive anti-ICOS monoclonal antibody MEDI-570 intravenously (IV) over 1-4 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 6 weeks for 12 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
City of Hope Comprehensive Cancer Center
Duarte, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States
Yale University
New Haven, Connecticut, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Kansas Clinical Research Center
Fairway, Kansas, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
...and 13 more locations
Incidence of toxicity and safety of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a sub-analysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.
Time frame: Up to 12 weeks after completion of study treatment
Maximum tolerated dose (MTD) of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Toxicity will be assessed using the NCI CTCAE, version 5.0.
Time frame: Up to 21 days
Recommended phase 2 dose of anti-inducible T-cell co-stimulator (ICOS) monoclonal antibody MEDI-570
Toxicity will be assessed using the NCI CTCAE, version 5.0.
Time frame: Up to 21 days
Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy
Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.
Time frame: Prior to dose on day 1, immediately after dose, and at 6 minutes, 24, 48 and 72 hours post dose of cycle 1 and cycle 2, and then on day 1 pre-dose of every subsequent cycle
Overall response rate
Assessed per the Revised Response Criteria for Malignant Lymphoma of the Lugano Classification. Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.
Time frame: Up to 36 weeks
Progression-free survival
Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.
Time frame: Up to 12 weeks after completion of study treatment
Immunogenicity
Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.
Time frame: Up to 36 weeks
Overall survival (OS)
Summary statistics, such as the mean, median, counts and proportion, will be used to describe patients' clinical characteristics. For all statistical tests, two-sided tests will be performed and no p-value adjustment performed due to the exploratory nature of these tests. A p-value of 0.05 or less will be considered statistically significant.
Time frame: Up to 12 weeks after completion of study treatment
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