Clinical Trial: Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Phase I Trial of MEDI-570 in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) Follicular Variant and Angioimmunoblastic T-Cell Lymphoma (AITL)
Brief Summary: 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 angioimmunblastic T-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Monoclonal antibodies, such as anti-ICOS monoclonal antibody MEDI-570, may block cancer growth in different ways by targeting certain cells.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To determine the safety, maximum tolerated dose and recommended phase II dose (RP2D) of MEDI-570 (anti-ICOS monoclonal antibody MEDI-570) in patients with refractory/relapsed peripheral T-cell lymphoma (PTCL) follicular variant and angioimmunoblastic T-cell lymphoma (AITL).
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.
TERTIARY OBJECTIVES:
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 3 weeks for up to 12 courses 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.
Sponsor: National Cancer Institute (NCI)
Current Primary Outcome:
- Incidence of toxicity and safety of MEDI-570, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 weeks after completion of study treatment ]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.
- Maximum tolerated dose (MTD) of MEDI-570 [ Time Frame: Up to 21 days ]Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events, version 4.0.
- Recommended phase 2 dose of MEDI-570 [ Time Frame: Up to 21 days ]Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Events, version 4.0.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Immunogenicity [ Time Frame: Up to 36 weeks ]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.
- Overall response rate, assessed per the Revised Response Criteria for Malignant Lymphoma of the Lugano Classification [ Time Frame: Up to 36 weeks ]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.
- Overall survival (OS) [ Time Frame: Up to 12 weeks after completion of study treatment ]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.
- Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy [ 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 ]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.
- Progression-free survival [ Time Frame: Up to 12 weeks after completion of study treatment ]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.
Original Secondary Outcome:
- Immunogenicity [ Time Frame: Up to 36 weeks ]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.
- Overall response rate, assessed per the Revised Response Criteria for Malignant Lymphoma of the Lugano Classification [ Time Frame: Up to 36 weeks ]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.
- Overall survival (OS) [ Time Frame: Up to 12 weeks after completion of study treatment ]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.
- Pharmacokinetics (PK), such as plasma concentration and PK parameters, of monoclonal antibody therapy [ Time Frame: Prior to dose on day 1, immediately after dose, and at 6, 24, 48 and 72 hours post dose of cycle 1 and cycle 2, and then on day 1 pre-dose of every subsequent cycle ]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.
- Progression-free survival [ Time Frame: Up to 12 weeks after completion of study treatment ]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.
Information By: National Cancer Institute (NCI)
Dates:
Date Received: August 10, 2015
Date Started: April 2016
Date Completion:
Last Updated: May 23, 2017
Last Verified: May 2017
