Availability of pulmonary function tests (PFTs – spirometry, diffusing capacity of the lungs for carbon monoxide [DLCO], +/- arterial blood gases) within 90 days prior to registration; patients with tracheotomy, etc, who are physically unable to perform PFTs are potentially still eligible if a study credentialed thoracic surgeon documents that the patient’s health characteristics would otherwise have been acceptable for eligibility as a high risk but nonetheless operable patient (in particular be eligible for sublobar resection)
Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
Participants with significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, carbon monoxide diffusing capability test (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates
Normal pulmonary functions tests (including carbon monoxide diffusing capability test [DLCO]) if there is a clinical indication for determination (dyspnea at rest, known requirement for supplemental oxygen); for subjects who do not have respiratory symptoms (no dyspnea at rest, oxygen [O2] saturation [sat] >= 93% on room air), full pulmonary function tests (PFTs) are NOT required
Carbon monoxide diffusing capability (DLCO) > 60% predicted (in children, oxygen [O2] saturation > 92% on room air)
Pulmonary: For patients > 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) > 40% and forced expiratory volume in one second (FEV1) > 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) > 50% predicted. For patients < 13.0 years of age unable to perform pulmonary function tests (PFT) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care (e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%)).
Pulmonary function tests: diffusing capacity of the lungs for carbon monoxide (DLco) (corrected for hemoglobin) and forced expiratory volume in 1 second (FEV1) >= 50% of predicted for the MAC arm, >= 40% of predicted for the RIC and RIC-MMF arm, and >= 30% predicted for the IOC arm; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation > 92% on room air; calculations will be based on the Unites States of America National Institutes of Health (USA-ITS-NIH) reference
Patients without respiratory symptoms (e.g. dyspnea at rest, known requirement for supplemental oxygen therapy) and who have an oxygen saturation > 92% on room air, will be eligible; for patients not meeting this criteria, pulmonary function tests will be performed to confirm that the diffusion capacity of the lung for carbon monoxide (DLCO)/alveolar volume (VA)/Adj is 50% of the normal predicted value corrected for hemoglobin and alveolar volume in order to meet eligibility\r\n* (For children who are unable to cooperate for pulmonary function test [PFT]s, the criterion is: No evidence of dyspnea at rest, no exercise intolerance and no requirement for supplemental oxygen therapy)
Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 60%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is < 92% on room air
Patients with impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (DLCO) < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air)
Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal or a pediatric patient who is unable to perform pulmonary function tests (PFTs) but has adequate pulmonary function
Pulmonary function\r\n* Baseline oxygen saturation > 92% on room air at rest \r\n* Patients with respiratory symptoms must have a diffusing capacity of the lungs for carbon monoxide (DLCO)/adjusted > 45%; for children who are unable to cooperate for pulmonary function tests (PFTs) they must not have dyspnea at rest or known requirement for supplemental oxygen
Major organ dysfunction defined as:\r\n* Creatinine clearance < 20 ml/min\r\n* Significant hepatic dysfunction (serum glutamic-oxaloacetic transaminase [SGOT] > 5 x upper limit of normal; bilirubin > 3.0 mg/dL)\r\n* Forced expiratory volume in 1 second (FEV1) of < 50% predicted or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% (patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing)
Adequate pulmonary function, defined as ? grade 1 dyspnea and saturated oxygen (SaO2) >= 92% on room air; if pulmonary function test (PFT)s are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in 1 second (FEV1) >= 50% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of >= 40% of predicted will be eligible
Patients must be without evidence of unstable or decompensated myocardial disease; and must have adequate pulmonary reserve evidenced by forced expiratory volume in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 35% predicted; carbon dioxide partial pressure (pCO2) < 50 mm Hg and partial pressure of oxygen (pO2) > 60 mm Hg on room air arterial-blood gas (ABG)
Oxygen saturation >= 90% on room air; pulmonary function test (PFT)’s required only if symptomatic or prior known impairment - must have pulmonary function > 50% corrected carbon monoxide diffusing capability (DLCO) and forced expiratory volume in 1 second (FEV1) (within 28 days of study registration)
Clinically significant pulmonary dysfunction, as determined by medical history and physical examination; patients with a history of pulmonary dysfunction must have pulmonary function tests with a forced expiratory volume in 1 second (FEV1) >= 60% of predicted and a diffusing capacity of the lung for carbon monoxide (DLCO) >= 55% (corrected for hemoglobin)
Oxygen saturation >= 90% on room air; pulmonary function tests (PFT’s) required only if symptomatic or prior known impairment - must have pulmonary function > 50% corrected diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1)
Oxygen saturation >= 90% on room air; pulmonary function tests (PFT’s) required only if symptomatic or prior known impairment - must have pulmonary function > 50% corrected diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1)
Oxygen saturation >= 90% on room air; if symptomatic or prior known impairment, pulmonary function >= 50% corrected diffusing capacity of the lungs for carbon monoxide (DLCO) and forced expiratory volume (FEV)1 is required, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
Adequate pulmonary function, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air; patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) >= 50% of predicted value or diffusing capacity of the lung for carbon monoxide (DLCO; corrected) >= 40% of predicted value
Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in 1 second (FEV1) of =< 65% or diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% will be excluded
Corrected diffusing capacity for carbon monoxide (DLCOcorr) >= 40% predicted, and absence of oxygen (O2) requirements; for children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with or without exercise should be attempted; if neither test can be obtained it should be clearly stated in the physician’s note
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in 1 second (FEV1) < 2.0 L or diffusion capacity of the lung for carbon monoxide (DLco) (corrected [corr] for hemoglobin [Hgb]) < 50% will be excluded
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Patients with any of the following pulmonary function abnormalities will be excluded: forced expiratory volume (FEV), < 30% predicted; diffusion capacity of the lung for carbon monoxide (DLCO), < 30% predicted (post-bronchodilator); oxygen saturation >= 92% on room air; arterial blood gas will be drawn if clinically indicated
Adequate pulmonary function defined as absence of oxygen (O2) requirements and one of the following:\r\n* Diffusion lung capacity for carbon monoxide (DLCO) corrected >= 70% mm Hg\r\n* DLCO corrected between 60% - 69% mm Hg and partial pressure of oxygen (pO2) >= 70 mm Hg\r\n* DLCO corrected between 50% - 59% mm Hg and pO2 >= 80 mm Hg\r\n* Pediatric patients unable to perform pulmonary function tests must have O2 saturation > 92% on room air; may not be on supplemental oxygen
Pulmonary: diffusing capacity of the lung for carbon monoxide (DLCO) > 30% predicted, and absence of oxygen (O2) requirements; for children that are not able to cooperate with pulmonary function tests (PFTs), a pulse oximetry with exercise should be attempted; if nether test can be obtained it should be clearly stated in the physician’s note
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, carbon monoxide diffusing capacity (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Respiratory failure (defined as oxygen saturation [SaO2] < 90% on room air; partial pressure of carbon dioxide [PCO2] > 45mmHg; or forced expiratory volume in one second [FEV1] <1.0 liter).
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in 1 second (FEV1) < 2.0 L or carbon monoxide diffusing capability (DLco) (correlation for hemoglobin [corr for Hgb]) < 75% will be excluded.
Within 14 days of study registration (30 days for pulmonary and cardiac): oxygen saturation >= 90% on room air with no symptomatic pulmonary disease. If symptomatic or prior known impairment single breath carbon monoxide diffusing capacity (DLCOc) or >= 40%.
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 60% of normal or carbon monoxide diffusing capacity (DLco) (corrected [corr] for hemoglobin [Hgb]) < 55% will be excluded.
TREATMENT: Patients with current or a history of interstitial lung disease, known severely impaired lung function (spirometry and carbon monoxide diffusing capability test (DLCO) 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air) or non-infectious pneumonitis will not be assigned treatment with everolimus or trametinib DMSO; symptoms should have resolved and course of antibiotics been completed for patients with a history of infectious pneumonitis to be eligible
Patients with any of the following pulmonary function abnormalities will be excluded: forced expiratory volume (FEV), < 30% predicted; diffusion capacity of the lung for carbon monoxide (DLCO), < 30% predicted (post-bronchodilator); partial pressure of oxygen (pO2) < 60 mm Hg or partial pressure of carbon dioxide (pCO2) >= 55 mm Hg on room air arterial blood gas
Patients with any of the following pulmonary function abnormalities: forced expiratory volume (FEV), < 30% predicted; diffusion capacity of the lungs for carbon monoxide (DLCO) < 30% predicted (post-bronchodilator); oxygen saturation less than 92% on room air
Pulmonary function: oxygen saturation >= 90% on room air and pulmonary function > 50% corrected diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1) testing required only if symptomatic or prior known impairment
Clinically significant pulmonary dysfunction, as determined by medical history and physical examination; patients with a history of pulmonary dysfunction must have pulmonary function tests with a forced expiratory volume in 1 second (FEV1) >= 60% of predicted and a diffusing capacity of the lung for carbon monoxide (DLCO) >= 55% (corrected for hemoglobin)
Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)
With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and carbon monoxide diffusing capability test (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O2) saturation < 92% on room air), or receiving supplementary continuous oxygen
Diffusing capacity of the lung for carbon monoxide (DLCO) >= 40% of the expected value corrected for alveolar volume and hemoglobin (hgb) for reduced intensity transplant and DLCO >= 55% for myeloablative regimen; for children who are unable to cooperate for pulmonary function tests (PFTs), the criterion is, no evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen therapy
Severely impaired lung function as defined as spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) that is < 50% of the normal predicted value and/or oxygen (02) saturation that is 88% or less at rest on room air
Any known uncontrolled underlying pulmonary disease by history, physical exam or if applicable pulmonary function tests (PFTs) (e.g. forced expiratory volume in 1 second [FEV1] or carbon monoxide diffusing capability [DLCO] 50% or less of predicted or oxygen [O2] saturation 88% or less at rest on room air)
Patients must not have any known uncontrolled underlying pulmonary disease (e.g. forced expiratory volume in 1 second [FEV1] or diffusion capacity of the lung for carbon monoxide [DLCO] 50% or less of predicted OR oxygen [O2] saturation 88% or less at rest on room air)
Normal pulmonary function tests (including diffusing capacity of the lungs for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen); Note: for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusion lung capacity [DLCO] corrected [corr] for hemoglobin [Hgb]) < 50% will be excluded.
Diffusing capacity for carbon monoxide (DLCO) >= 45% predicted corrected for hemoglobin; for children =< 7 years of age who unable to perform the pulmonary function test, an oxygen (O2) saturation of >= 92% on room air
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in 1 second (FEV1) < 2.0 L or diffusion capacity of the lungs for carbon monoxide (DLCO) (corrected for Hb) < 50% will be excluded
Forced expiratory volume in 1 second (FEV1) >= 50% or diffusion capacity of the lung for carbon monoxide (DLCO) (hemoglobin [Hb]) >= 40% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD; for pediatric patients < 7 years old, pulmonary function testing will not be required; rather, pediatric patients < 7 years old who have pulmonary symptoms will be evaluated by a pulmonologist
Patients must not have any known uncontrolled underlying pulmonary disease or severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection; uncontrolled hypertension) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusion capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 60% predicted; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is < 92% on room air
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLCO), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Oxygen saturation >= 90% on room air and diffusing capacity of the lung for carbon monoxide corrected (DLCOcor) >= 40%
Pulmonary function of diffusing capacity of the lung for carbon monoxide (DLCO) adjusted for alveolar volume (adj/VA) and forced expiratory volume in one second (FEV1) >= 60% of normal indices for age and height unless the patient has a likely acute reversible etiology of decline and then DLCO adj/VA >= 30% of normal; pediatric patients unable to complete pulmonary function tests (PFTs) may be enrolled as per enrolling institution standard operating procedure (SOP) for recipient guidelines
Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol\r\n* Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (02) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) < 50% will be excluded
Pulmonary function: > 40% corrected diffusing capacity of carbon monoxide (DLCO) and forced expiratory volume in one second (FEV1) (oxygen saturation [> 92%] can be used in child where pulmonary function tests [PFT's] cannot be obtained)
Corrected diffusing capacity of the lung for carbon monoxide (DLCOcorr) > 50% of normal, (oxygen saturation [> 92%] can be used in child where pulmonary function tests [PFT’s] cannot be obtained)
Clinically significant pulmonary symptoms and signs, any active pulmonary or respiratory infection at enrollment, pulmonary infiltrates on screening CT scan of the chest that are associated with symptoms (including dyspnea), resting or exercise arterial oxygen saturation (SpO2) less than (<) 90 percent (%), requirement for supplementary oxygen at rest or exercise (either continuously or intermittently), moderate (40%-60% predicted) or severe (<40% predicted) decreased diffusing capacity for carbon monoxide (DLCO) or mild (>60% </= lower limit of normal [LLN]% predicted) decrease with clinically significant symptoms
Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have at least one of the following: congestive heart failure or ejection fraction less than or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter (mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2; prior or current malignancy that does not require concurrent treatment; unresolved infection; comorbidity that, in the Investigator's opinion, makes the participant unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
Chest x-ray (CXR) or computed tomography CT within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema. If results are questionable, patients should have additional lung function testing to exclude clinically relevant restriction or obstruction. Patients must have a forced expiratory volume (FEV-1) and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) of at least 65% and 50% of expected, respectively.
Patients must have adequate pulmonary reserve evidenced by predicted post-operative forced expiratory volume in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) equal to or greater than 40% predicted; partial pressure of carbon dioxide measurement (pCO2) less than 50 mm Hg and partial pressure of oxygen measurement (pO2) greater than 60 mm Hg on room air arterial blood gas measurement (ABG); and be on no immunosuppressive medications except inhaled corticosteroids
Carbon monoxide diffusing capability test (DLCO) > 60% predicted and in children- room air oxygen saturation > 92%