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

NCT03972943 | Terminated Early Phase 1 DMC

• 3 other identifiers: HCI114917NCI-2019-01690P30CA042014
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

CALR Gene Mutation; Essential Thrombocythemia; JAK2 Gene Mutation; MPL Gene Mutation; Obstructive Sleep Apnea Syndrome; Polycythemia Vera

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Proportion of patients with a diagnosis of obstructive sleep apnea (OSA)

  During the OSA screening

• Leucocytes, platelets, red cell counts, and tumor necrosis factor (TNF) analysis

  Baseline, after 3 months, and after 6 months on trial

• Thrombotic and inflammatory marker levels for all patients

  Baseline, after 3 months, and after 6 months on trial

Study Arms (2)

Cohort I (observation)

ACTIVE COMPARATOR

Patients not diagnosed with OSA undergo observation for 6 months.

Other: Patient Observation; Other: Questionnaire Administration

Cohort II: (CPAP treatment)

EXPERIMENTAL

Patients diagnosed with OSA and prescribed a CPAP machine for treatment receive continuous treatment with CPAP for 6 months.

Procedure: Continuous Positive Airway Pressure; Other: Questionnaire Administration

Interventions

Continuous Positive Airway Pressure PROCEDURE

Receive CPAP treatment

Also known as: Continuous positive airway pressure (CPAP), CPAP

Cohort II: (CPAP treatment)

Patient Observation OTHER

Undergo observation

Also known as: Active Surveillance, deferred therapy, expectant management, observation, Watchful Waiting

Cohort I (observation)

Questionnaire Administration OTHER

Ancillary studies

Cohort I (observation); Cohort II: (CPAP treatment)

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Veterans Administration Medical Center

Salt Lake City, Utah, 84148, United States

Location

MeSH Terms

Conditions

Thrombocythemia, Essential; Sleep Apnea, Obstructive; Polycythemia Vera

Interventions

Continuous Positive Airway Pressure; Watchful Waiting; Observation

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques

Study Officials

• Krishna Sundar

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: June 4, 2019
• Study Start: May 15, 2019
• Primary Completion: July 28, 2023
• Study Completion: July 28, 2023
• Last Updated: January 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)