CPAP in Treating Obstructive Sleep Apnea in Patients With Polycythemia Vera or Essential Thrombocythemia

Modulation of Morbidity and Disease Progression in Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Patients With Obstructive Sleep Apnea (OSA) by CPAP

This early phase I trial studies how well the use of a continuous positive airway pressure (CPAP) machine works in treating obstructive sleep apnea in patients with polycythemia vera or essential thrombocythemia. Obstructive sleep apnea is a condition where a person stops breathing during sleep, and is estimated to affect 30 to 50 percent of patients with polycythemia vera or essential thrombocythemia. A patient with obstructive sleep apnea typically snores, has disrupted sleep, experiences morning headaches, and has daytime sleepiness. Patients diagnosed with obstructive sleep apnea are typically treated with a device called CPAP. The CPAP provides pressurized air that keeps upper air passages open during sleep and may prevent them from narrowing or collapsing as occurs during snoring or sleep apnea.

Study Overview

• Status: Terminated
• Conditions: Obstructive Sleep Apnea Syndrome; Polycythemia Vera; Essential Thrombocythemia; CALR Gene Mutation; JAK2 Gene Mutation; MPL Gene Mutation
• Intervention / Treatment: Other: Questionnaire Administration; Other: Patient Observation; Procedure: Continuous Positive Airway Pressure

Detailed Description

PRIMARY OBJECTIVES:

I. To understand effects of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) on the course of polycythemia vera/essential thrombocythemia (PV/ET).

EXPLORATORY OBJECTIVES:

I. To estimate prevalence of OSA in patients with myeloproliferative neoplasms. II. To understand effects of CPAP for sleep apnea on the course of myeloproliferative neoplasms (MPNs).

III. To correlate OSA severity with thrombotic and inflammatory marker values in patients with PV/ET at baseline.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I (OBSERVATIONAL COHORT): Patients not diagnosed with OSA undergo observation for 6 months.

COHORT II (TREATMENT COHORT): Patients diagnosed with OSA and prescribed a CPAP machine for treatment receive continuous treatment with CPAP for 6 months.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Braxton Smith; Phone Number: 801-213-8431; Email: Braxton.Smith@hci.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Administration Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• OSA SCREENING ELIGIBILITY CRITERIA: Documented diagnosis of essential thrombocythemia or polycythemia vera by either 2008 WHO criteria or 2016 WHO Criteria prior to screening.
• OSA SCREENING ELIGIBILITY CRITERIA: For subjects receiving therapy for PV or ET (i.e. hydroxyurea, peginterferon, etc.): Patients must be on a stable dose for >= 28 days prior to study entry and expected to remain on a stable dose for the duration of trial participation. It is anticipated that during the 6 month duration of study, there will not be any dose modification of hydroxyurea or interferon and this will be communicated to treating providers and patient during enrollment into the trial. However, clinically indicated dose modification of PV/ET therapy while on trial will not necessitate CPAP study discontinuation.
• OSA SCREENING ELIGIBILITY CRITERIA: Subject must have =< 20.0 pack-year smoking history OR have quit smoking => 3 years ago and do not have any current symptoms of COPD and/or have normal pulmonary function tests.
• OSA SCREENING ELIGIBILITY CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• OSA SCREENING ELIGIBILITY CRITERIA: Negative serum or urine pregnancy test at screening for women of childbearing potential.
• OSA SCREENING ELIGIBILITY CRITERIA: Highly effective contraception for both male and female subjects from study enrollment through treatment, and for at least 3 months after last study treatment administration if the risk of conception exists.
• OSA SCREENING ELIGIBILITY CRITERIA: Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
• OSA SCREENING ELIGIBILITY CRITERIA: Able to read and complete required study questionnaires.
• TREATMENT ELIGIBILITY CRITERIA: Eligible for OSA Screening Component portion of this trial.
• TREATMENT ELIGIBILITY CRITERIA: Diagnosed OSA with Sleep Study score >= 5.
• TREATMENT ELIGIBILITY CRITERIA: Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference and Gender (STOP-BANG) screening questionnaire score >= 3.
• TREATMENT ELIGIBILITY CRITERIA: Willingness to comply with required CPAP compliance rate of >= 4hrs/day for 70% of days over 6 months of CPAP treatment.
• TREATMENT ELIGIBILITY CRITERIA: Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

• OSA SCREENING ELIGIBILITY CRITERIA: Use of JAK2 inhibitors within 6 months prior to registration.
• OSA SCREENING ELIGIBILITY CRITERIA: Previous or current use of TNF inhibitors.
• OSA SCREENING ELIGIBILITY CRITERIA: Prior substantial, prolonged use of CPAP or alternative therapy for OSA, including oxygen. No more than 6 monthsof continuous therapy with CPAP in the last 5 years will be allowed.
• OSA SCREENING ELIGIBILITY CRITERIA: Autoimmune disease requiring concurrent use of immunomodulatory, including rheumatologic disorders.
• OSA SCREENING ELIGIBILITY CRITERIA: Prior invasive cancer (except nonmelanoma skin cancer) unless disease free for at least 2 years or life expectancy without treatment is greater than 2 years, e.g., low risk localized prostate cancer.

• OSA SCREENING ELIGIBILITY CRITERIA: The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

  • Cardiovascular disorders:

    • Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
    • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
    • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months of screening. Patients receiving anti-coagulant therapy for previous thromboembolic event will be allowed to enroll on study.

  • Other clinically significant disorders that would preclude safe study participation.

    • End stage Renal disease
    • Advanced liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
    • Active (acute or chronic) or uncontrolled severe infection
• OSA SCREENING ELIGIBILITY CRITERIA: Known history of human immunodeficiency virus (HIV), chronic hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
• TREATMENT ELIGIBILITY CRITERIA: Use of JAK2 inhibitors within 6 months of registration.
• TREATMENT ELIGIBILITY CRITERIA: Previous or current use of TNF inhibitors.
• TREATMENT ELIGIBILITY CRITERIA: Prior use of CPAP or alternative therapy for OSA, including oxygen.
• TREATMENT ELIGIBILITY CRITERIA: Autoimmune disease requiring concurrent use of immunomodulatory, including rheumatologic disorders.
• TREATMENT ELIGIBILITY CRITERIA: Prior invasive cancer (except nonmelanoma skin cancer) unless disease free for at least 2 years or life expectancy without treatment is greater than 2 years, e.g., low risk localized prostate cancer.

• TREATMENT ELIGIBILITY CRITERIA: The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

  • Cardiovascular disorders:

    • Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
    • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
    • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months of screening. Patients receiving anti-coagulant therapy for previous thromboembolic event will be allowed to enroll on study.

  • Other clinically significant disorders that would preclude safe study participation.

    • End stage Renal disease
    • Advanced liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
    • Active (acute or chronic) or uncontrolled severe infection
• TREATMENT ELIGIBILITY CRITERIA: Known history of HIV, chronic hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort I (observation); Patients not diagnosed with OSA undergo observation for 6 months.	Other: Questionnaire Administration; Ancillary studies; Other: Patient Observation; Undergo observation; Other Names: observation; Active Surveillance; deferred therapy; expectant management; Watchful Waiting
Experimental: Cohort II: (CPAP treatment); Patients diagnosed with OSA and prescribed a CPAP machine for treatment receive continuous treatment with CPAP for 6 months.	Other: Questionnaire Administration; Ancillary studies; Procedure: Continuous Positive Airway Pressure; Receive CPAP treatment; Other Names: CPAP; Continuous positive airway pressure (CPAP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)	Will be tested at the two-sided 0.025 significance level to provide overall control of the type I error for the co-primary endpoints at 0.05. The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.	Baseline, after 3 months, and after 6 months on trial
Change in JAK2 V617F allele burden	Will be tested at the two-sided 0.025 significance level to provide overall control of the type I error for the co-primary endpoints at 0.05. The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.	Baseline, after 3 months, and after 6 months on trial

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with a diagnosis of obstructive sleep apnea (OSA)	Assessed by Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference and Gender (STOP-BANG) questionnaire. The proportion of patients whose results indicate a diagnosis of OSA will be calculated. All patients with a diagnosis of OSA, regardless of whether they are enrolled to the treatment component of the study, will be counted towards the assessment of prevalence. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.	During the OSA screening
Leucocytes, platelets, red cell counts, and tumor necrosis factor (TNF) analysis	The endpoints will be summarized by mean, median, range, standard deviation, interquartile range and boxplots. Scatterplots will be used to show bivariate associations. An assessment of normality will be made prior to statistical testing. Paired t tests will be used to analyze endpoints that are sufficiently Gaussian in distribution. Paired Wilcoxon tests will be used to analyze variables that are highly skewed or otherwise non-Gaussian in distribution.	Baseline, after 3 months, and after 6 months on trial
Thrombotic and inflammatory marker levels for all patients	Will be measured in blood samples taken from all patients. OSA-related adverse events reported in the Treatment Cohort at these timepoints will be correlated with these marker levels. Pearson or Spearman correlation will be used to assess correlation between thrombo-inflammatory markers and oximetric abnormalities.	Baseline, after 3 months, and after 6 months on trial

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Krishna Sundar, Huntsman Cancer Institute/ University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): July 28, 2023

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Signs and Symptoms, Respiratory; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: HCI114917 (Other Identifier: Huntsman Cancer Institute/University of Utah); P30CA042014 (U.S. NIH Grant/Contract); NCI-2019-01690 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No