This phase I trial studies the side effects and best dose of ipilimumab and how well it works in treating patients with high-risk myelodysplastic syndrome or acute myeloid leukemia that has come back or no longer responds to treatment. Monoclonal antibodies, such as ipilimumab, may interfere with the ability of cancer cells to grow and spread.
PRIMARY OBJECTIVES: I. Evaluate the safety and toxicity associated with the administration of ipilimumab in terms of dose limiting toxicities (DLT), and maximally-tolerated dose (MTD) in a cohort of patients with high risk myelodysplastic syndrome who failed hypomethylating therapy, and patients with acute myeloid leukemia (AML) who underwent induction therapy but are not planned for further intensive chemotherapy. (Dose-escalation) II. Determine the optimal dose of ipilimumab for the dose-expansion phase of the trial. (Dose-escalation) III. Better define immunologic profiles associated with ipilimumab use in terms of regulatory T-cells (T-regs) dynamic changes in 2 separate cohorts of myelodysplastic syndrome (MDS) and AML patients at the optimal dose level. (Dose-expansion) IV. Obtain preliminary efficacy data of ipilimumab in terms of complete response (CR), partial response (PR), and hematological improvement (HI) in both cohorts. (Dose-expansion) SECONDARY OBJECTIVES: I. Define immunologic profiles associated with ipilimumab use in terms of T-regs dynamic changes at different dose levels. (Dose-escalation) II. Define toxicity profiles of ipilimumab at the optimal dose in both patient cohorts. (Dose-expansion) III. Obtain preliminary data on potential correlations between noted ipilimumab-induced immunologic changes and observed toxicity and clinical responses. (Dose-expansion) OUTLINE: This is a dose-escalation study. INDUCTION: Patients receive ipilimumab intravenously (IV) on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning 12 weeks after last dose of induction ipilimumab, patients receive ipilimumab IV on day 1. Treatment repeats every 12 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at least monthly for 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Given IV
Correlative studies
Yale University
New Haven, Connecticut, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Baylor University Medical Center
Dallas, Texas, United States
Texas Oncology at Baylor Irving Cancer Center
Irving, Texas, United States
Incidence of DLT of ipilimumab by grading and tabulation using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: 42 days
Changes in percentages of T-regs
Changes in T-regs percentages at designated time points will be correlated with clinical responses and toxicity after ipilimumab. The response will be modeled as the vector for each individual from multiple measures of T-regs percentages as a function of time and group (MDS vs AML). T-regs percentages will be transformed onto the log-scale, and t tests will be used to compare groups at specific time points. Regression models that use generalized estimating equations will be implemented when all time points are considered to account for within-subject correlation of repeated measures.
Time frame: Baseline to up to 6 months post-treatment
Efficacy as defined by the International working group 2006 criteria for CR, PR, HI
The agreement between immunologic and clinical response will be evaluated with McNemar's test, separately by cohort. Rates of CR, PR, and HI will be summarized separately by cohort and reported with an exact 95% confidence interval.
Time frame: Up to 6 months post-treatment
Progression free survival (PFS)
Median PFS will also be reported with a 95% confidence interval. As an exploratory analysis, survival endpoints will be descriptively compared with a log-rank test between patients who do and do not have an immunologic response, separately by cohort.
Time frame: From start of study to progression or death, assessed up to 6 months post-treatment
Overall survival (OS)
Median OS will also be reported with a 95% confidence interval. As an exploratory analysis, survival endpoints will be descriptively compared with a log-rank test between patients who do and do not have an immunologic response, separately by cohort.
Time frame: From start of study to death, assessed up to 6 months post-treatment
Rate of prior use of demethylating agents
Will be descriptively compared between patients who have a clinical response and by toxicity with Fisher's exact tests.
Time frame: Up to 6 months post-treatment
Rate of pre-treatment CR
Will be descriptively compared between patients who have a clinical response and by toxicity with Fisher's exact tests.
Time frame: Up to 6 months post-treatment
Lymphocyte counts
Will be summarized and compared between response and toxicity groups with either t tests or Wilcoxon rank sum tests.
Time frame: Baseline
T cell receptor diversity
Will be summarized and compared between response and toxicity groups with either t tests or Wilcoxon rank sum tests.
Time frame: Baseline
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