The main purpose of this investigational research study is to determine how safe and tolerable the study drug, MEDI4736 (Durvalumab), is in patients with myelofibrosis (MF). The study drug belongs to a group of drugs called immune checkpoint inhibitors, which have shown promise in other forms of cancer, such as melanoma and lung cancer. One of the effects that this drug has is to activate the patient's own natural immune system. The purpose of this study is to examine the safety and tolerability of the study drug, to study how effective it is at treating patients with myelofibrosis, and to explore how certain markers in the patient's blood and/or bone marrow may be affected by the study drug.
PRIMARY OBJECTIVES: I. To determine the safety profile of anti-programmed cell death 1 ligand 1 (PDL1) therapy in patients with myelofibrosis. SECONDARY OBJECTIVES: I. Changes in MF symptom burden. II. Changes in spleen size. III. Blood and/or bone marrow samples. TERTIARY OBJECTIVES: I. To determine the rate of lymphocyte subset response to anti-PDL1 therapy, as measured by the percent increase in cluster of differentiation (CD)4+CD25+PD-L1+ T-lymphocytes and CD4+CD62L+CD127+ T lymphocytes in post-treatment peripheral blood samples. II. To characterize changes in the cytokine profile in response to anti-PDL1 therapy. III. To measure soluble PDL1 by enzyme-linked immunosorbent assay (ELISA) in post-treatment blood and/or bone marrow samples and programmed cell death-1 (PD1)/PDL1 by immunohistochemistry on bone marrow samples and correlate with treatment response. OUTLINE: Patients receive durvalumab intravenously (IV) over approximately 1 hour on day 1. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD), no new inter-current illness, and no unacceptable toxicity, may continue treatment beyond 3 courses. Patients will be followed every 3 months for up to two years starting from Day 1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given IV
Correlative studies
Northwestern University
Chicago, Illinois, United States
Incidence of Adverse Events
To determine the safety profile of anti-PDL1 therapy in patients with myelofibrosis, adverse events will be assessed by number, frequency, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Time frame: Up to 2 years
Changes in MF symptom burden
Changes in MF symptom burden will be assessed using the validated Patient Reported Outcome tool called the Myeloproliferative Neoplasm (MPN)-Symptom Assessment Form (SAF).
Time frame: Baseline up to 2 years
Changes in spleen size
Change in spleen size will be assessed by physical examination (palpation) OR ultrasound as part of standard of care.
Time frame: Baseline up to 2 years
Response to anti-PDL1 treatment in blood
Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by blood samples.
Time frame: Up to 2 years
Response to anti-PDL1 treatment in bone marrow
Response to anti-PDL1 treatment will be defined in accordance with the revised/modified International Working Group (IWG) Response Criteria and will be assessed by bone marrow samples.
Time frame: Up to 2 years
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