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

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ClinicalTrials.gov Identifier: NCT03972943
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : August 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Utah

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.

Condition or disease Intervention/treatment Phase
CALR Gene Mutation Essential Thrombocythemia JAK2 Gene Mutation MPL Gene Mutation Obstructive Sleep Apnea Syndrome Polycythemia Vera Procedure: Continuous Positive Airway Pressure Other: Patient Observation Other: Questionnaire Administration Early Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modulation of Morbidity and Disease Progression in Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Patients With Obstructive Sleep Apnea (OSA) by CPAP
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : May 1, 2024
Estimated Study Completion Date : May 2025


Arm Intervention/treatment
Active Comparator: Cohort I (observation)
Patients not diagnosed with OSA undergo observation for 6 months.
Other: Patient Observation
Undergo observation
Other Names:
  • Active Surveillance
  • deferred therapy
  • expectant management
  • observation
  • Watchful Waiting

Other: Questionnaire Administration
Ancillary studies

Experimental: Cohort II: (CPAP treatment)
Patients diagnosed with OSA and prescribed a CPAP machine for treatment receive continuous treatment with CPAP for 6 months.
Procedure: Continuous Positive Airway Pressure
Receive CPAP treatment
Other Names:
  • Continuous positive airway pressure (CPAP)
  • CPAP

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Change in Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS) [ Time Frame: Baseline, after 3 months, and after 6 months on trial ]
    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.

  2. Change in JAK2 V617F allele burden [ Time Frame: Baseline, after 3 months, and after 6 months on trial ]
    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.


Other Outcome Measures:
  1. Proportion of patients with a diagnosis of obstructive sleep apnea (OSA) [ Time Frame: During the OSA screening ]
    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.

  2. Leucocytes, platelets, red cell counts, and tumor necrosis factor (TNF) analysis [ Time Frame: Baseline, after 3 months, and after 6 months on trial ]
    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.

  3. Thrombotic and inflammatory marker levels for all patients [ Time Frame: Baseline, after 3 months, and after 6 months on trial ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • OSA SCREENING ELIGIBILITY CRITERIA: Diagnosed essential thrombocythemia or polycythemia vera by 2016 World Health Organization (WHO) criteria.
  • OSA SCREENING ELIGIBILITY CRITERIA: Polycythemia vera: Patients must meet criteria a, b, and c OR a, b, and d:

    • a. Hemoglobin > 16.5 g/dL (men), hemoglobin > 16.0 g/dL (women), hematocrit > 49% (men), hematocrit > 48% (women) or increased red cell mass (RCM)
    • b. Bone marrow (BM) biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
    • c. Presence of JAK2 or JAK2 exon 12 mutation
    • d. Subnormal serum erythropoietin level.
  • OSA SCREENING ELIGIBILITY CRITERIA: Essential thrombocythemia: Patients must meet criteria a, b, c, and d OR a, b, c, and e

    • a. Platelet count >= 450 ? 10^9 /L
    • b. BM biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant left-shift of neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers
    • c. Not meeting WHO criteria for BCR-ABL1 + chronic myelogenous leukemia (CML), polycythemia vera (PV), primary myelofibrosis (PMF), myelodysplastic syndrome (MDS), or other myeloid neoplasms
    • d. Presence of JAK2, CALR or MPL mutation
    • e. Presence of a clonal marker (e.g., abnormal karyotype) or absence of evidence for reactive thrombocytosis.
  • 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.
  • 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.
  • 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: Previous or current use of JAK2 inhibitors.
  • OSA SCREENING ELIGIBILITY CRITERIA: Previous or current use of TNF inhibitors.
  • OSA SCREENING ELIGIBILITY CRITERIA: Prior use of CPAP or alternative therapy for OSA, including oxygen.
  • 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: Previous or current use of JAK2 inhibitors.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03972943


Contacts
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Contact: Catherine Cromar 801-213-5652 Catherine.cromer@hci.utah.edu

Locations
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United States, Utah
Huntsman Cancer Institute/University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Catherine Cromar    801-213-5652    Catherine.cromar@hci.utah.edu   
Principal Investigator: Krishna Sundar         
Sponsors and Collaborators
University of Utah
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Krishna Sundar Huntsman Cancer Institute/ University of Utah

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Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT03972943     History of Changes
Other Study ID Numbers: HCI114917
NCI-2019-01690 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HCI114917 ( Other Identifier: Huntsman Cancer Institute/University of Utah )
P30CA042014 ( U.S. NIH Grant/Contract )
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019

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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
Additional relevant MeSH terms:
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Thrombocytosis
Thrombocythemia, Essential
Polycythemia Vera
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Polycythemia
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders