Severe organ dysfunction unrelated to underlying GVHD, including:
Serum creatinine < 2 mg/dl; NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration
Have metastatic breast cancer with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
Major organ system dysfunction including (but not limited to): New York Heart Association class III or IV, pulmonary disease requiring the use of inhaled steroids or bronchodilators, renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction which would impair patient’s ability to participate in the trial
Any subject with a history of significant renal, hepatic, pulmonary dysfunction, or cardiac dysfunction or on treatment to support cardiac dysfunction
Cardiopulmonary dysfunction
Evidence of renal or liver dysfunction at screening
Prior treatment with clofarabine within 6 months or history of clofarabine-induced liver dysfunction
Have a history of cardiac dysfunction including:
known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis
Patients with organ dysfunction
Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as
Liver dysfunction (or digestive involvement with protein loss)
Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as defined in Table XI (see Section 10.3.1).
Patients with evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist
No major organ dysfunction precluding transplantation.
Significant cardiopulmonary dysfunction
Acute neurological dysfunction as a result of bone metastasis.
Significant organ dysfunction, not meeting inclusion criteria
Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction
Subject has evidence of hepatic dysfunction defined as:
Significant renal, hepatic, or bone marrow organ dysfunction.
No major organ dysfunction precluding transplantation
Subjects must not have evidence of cerebellar dysfunction at baseline or during prior cytarabine therapy
No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes
If organ dysfunction is thought to be related to the HLH process this must be clearly documented in the chart and the patients may be enrolled on study irrespective of creatinine and bilirubin levels
Patients should have no evidence of immune dysfunction as listed below
Significant organ dysfunction defined as:
Patients with systemic infections and/or organ dysfunction mandating a reduced intensity conditioning regimen are also excluded
Patients with renal dysfunction or veno-occlusive disease are eligible
Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient’s ability to endure known side effects of cytokine release syndrome or neurological toxicity
Hepatic, renal, or bone marrow dysfunction as detailed above
Severe liver dysfunction or pulmonary insufficiency
Severe liver dysfunction or pulmonary insufficiency
Patients with significant renal (creatinine [Cr.] > 1.5 mg/dl or creatinine clearance < 40 cc/min) or hepatic (bilirubin > 2.5 u) dysfunction not due to tumor involvement will not be eligible to receive DA-EPOCH-R chemotherapy
Patient has laboratory estimations indicating organ system dysfunction:
Clinically significant GVHD or organ dysfunction where chemotherapy specified by protocol cannot be given
Patients with all degrees of renal dysfunction are allowed including patients on hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined below:
Patients with both hepatic and renal dysfunction will also be excluded
Patients receiving medications for treatment of left ventricular systolic dysfunction
Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: \r\n * Renal insufficiency as defined by an estimated glomerular filtration rate (GFR) < 60 mL/minute\r\n * Cardiac dysfunction as defined by symptomatic coronary artery disease, congestive heart failure, valvular heart disease, cardiomyopathy, uncontrolled arrhythmia(s), or left ventricular ejection fraction < 50%\r\n * Pulmonary dysfunction that poses a risk of mortality after transplant, defined as pulmonary disease-moderate, using pre-transplant pulmonary function testing per the Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Manual\r\n * Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension\r\n * Marrow dysfunction that poses a risk of peri-transplant mortality, defined as an absolute neutrophil count or lymphocyte count below the lower limit of normal, or a platelet count below 50,000/mm^3\r\n * Poorly controlled hypertension despite appropriate therapy, defined as a diastolic blood pressure greater than 90 mm Hg while on therapy\r\n * Neurologic dysfunction that affects activities of daily living and medical care\r\n * Poorly controlled diabetes mellitus, defined as persistent hyperglycemia despite therapy or recurrent hypoglycemia while on therapy\r\n * Extreme protein-calorie malnutrition defined by body mass index < 18 kg/m^2 and unintentional weight loss (3 kg in the last month or 6 kg in the last 6 months)
Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification
In the opinion of the investigator do not require rapid cytoreduction due to bulky disease (e.g. painful lymphadenopathy or organomegaly, or impending end-organ dysfunction
Patients with normal, mild or moderate hepatic dysfunction are eligible
With hepatic dysfunction as evidenced by total bilirubin > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
Patients with significant hepatic dysfunction (not meeting liver function tests [LFT] eligibility criteria)
Patients should have no evidence of immune dysfunction
As patients with steroid refractory acute GvHD are quite ill with multiple abnormal labs and organ dysfunction, there are no explicit laboratory values or degree of organ dysfunction that specifically preclude enrollment on this study; baseline lab studies will be obtained and followed throughout this trial as the standard of care for patients with GvHD
Subject has any other organ dysfunction (CTCAE version 4.03 Grade 4) that will interfere with the administration of the therapy according to this protocol.
Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol.
Severe organ dysfunction unrelated to underlying GVHD, including:
Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
EXCLUSION FOR TREATMENT: Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient’s ability to endure known side effects of cytokine release syndrome or neurologic toxicity
Any other concomitant serious illness or organ system dysfunction as per investigator assessment
Use of erectile dysfunction drugs (e.g., Cialis, Viagra) within 14 days prior to treatment or during study
Cardiovascular dysfunction or Respiratory Failure due to sepsis.
Cardiac disease or dysfunction.
No evidence of significant cardiac or pulmonary dysfunction
Any serious ongoing condition, such as an untreated infection or organ dysfunction
Subjects with severe (immediately life threatening) and recent (occurring within the last 3 months) cardiac dysfunction, pulmonary dysfunction, esophageal variceal bleeding, hemorrhagic strokes, or intracranial hemorrhage are not eligible for study participation
Hepatic dysfunction as evidenced by elevated transaminases
No evidence of significant cardiac or pulmonary dysfunction
Cardiopulmonary dysfunction as defined by protocol
Have a history of liver or renal dysfunction
Significant co-morbidity indicated by major organ system dysfunction
Patients with renal or liver dysfunction due to organ infiltration with CLL may be eligible after discussion with the study chairman
Failure of 2 of the following drugs: interferon-beta1b, interferon beta 1a, and glatiramer acetate; failure is defined by new or progressive physical signs and symptoms that impair activities of daily living; such changes include cognitive decline, vision loss, swallowing dysfunction, limb weakness, limb plasticity, bowel or bladder dysfunction, and coordination or gait dysfunction; these clinical changes should be supported by new or expanding lesions on MRI scanning consistent with disease progression
Creatinine < 2 mg %; patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman
Bilirubin < 2 mg %; patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman
Serious organ dysfunction
Significant hepatic dysfunction, renal dysfunction, or metabolic derangement that precludes full-dose chemotherapy at the specified starting doses
Patient with significant cardiac, renal or hematologic or pulmonary dysfunction
Any organ dysfunction thought to be secondary to disease will be considered separately and the patient will be included at the investigators discretion
History of symptomatic pulmonary dysfunction
Significant cardiac dysfunction:
Known systolic or diastolic dysfunction or heart failure
No evidence of significant cardiac or pulmonary dysfunction
Severe organ dysfunction manifested during screening period:
Laboratory evidence of hepatic dysfunction indicated by any of the following:
Significant organ dysfunction.
Hepatic dysfunction defined as MELD Score > 12.
History of serious cardiac dysfunction
Significant organ dysfunction deemed to be inappropriate for autologous transplantation
Subject has concurrent severe or uncontrolled medical disease or organ system dysfunction which, in the opinion of the Investigators, would limit life expectancy to < 3 months.
Serious myocardial dysfunction defined as ultrasound-determined LVEF < 45% of predicted institutional normal value.
Liver/renal dysfunction
Any medications for treatment of left ventricular systolic dysfunction.
History of significant cardiac dysfunction
Diastolic dysfunction felt to contribute to any clinical sign or symptom.
In hepatic dysfunction group, patients with hepatic dysfunction who have Gilbert's syndrome. Patients signs of encephalopathy (altered brain function).
Evidence of at least 1 new onset organ dysfunction
No specific organ function parameters are required; however, significant abnormalities should be discussed with the study PI (this is especially the case for significant renal dysfunction)
Severe hepatic dysfunction accompanied by coagulopathy definition:\r\n* Known liver disease AND\r\n* International normalized ratio (INR) > 1.5 (except for patients on anticoagulants) AND\r\n* Platelet count < 100,000/uL without other obvious cause
Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
History of nasal or sinus anomalies or dysfunction e.g. allergic or infectious rhinitis
Hepatic dysfunction (elevated transaminases or bilirubin > 3 times normal), drawn within 28 days of consent
Regarding non-hematologic organ function, no specific criteria for non-hematologic organ function are specified; however, if moderate-to-severe (major) organ function is present, such should be discussed with the PI, as various degrees of non-hematologic organ dysfunction may compromise either (or both) toxicity and response evaluations; also, if there is concern regarding potential reversibility of any specific organ dysfunction, this issue should also be addressed by consultation with an appropriate sub-specialist
Renal dysfunction (creatinine [Cr] > 1.8)
Individuals with co-morbid acute or untreated psychiatric symptoms (e.g., psychosis) or neurologic dysfunction will be excluded
Patients unable to use audio media due to auditory dysfunction
Presence of erectile dysfunction symptoms
Patients with severe organ dysfunction\r\n* On dialysis\r\n* Requiring oxygen (O2) at more than 2 l/min\r\n* Uncontrolled arrhythmia or heart failure\r\n* Veno-occlusive disease (sinusoidal obstruction syndrome)
Patients diagnosed with chronic disease/illness precluding their participation (i.e., diabetics receiving insulin, myocardial infarction or unstable angina within previous 6 months, chronic hepatitis, rheumatoid disease, renal or hepatic disease/dysfunction)
History of known renal dysfunction
Severe organ dysfunction.
Suitable candidate for surgery (meets appropriate performance status, no significant cardiac/renal/hepatic dysfunction)
Have renal dysfunction
History of hepatitis or liver dysfunction
Current or history of hepatic dysfunction
Untreated or uncontrolled cardiovascular disease or other symptomatic cardiac dysfunction
Patients must not have evidence of significant hematologic, renal, or hepatic dysfunction
History of known renal dysfunction
Renal dysfunction for which cisplatin dose would be considered unsafe
Patients with history or evidence of cardiac dysfunction
Sinus node dysfunction
Have a history of liver or renal dysfunction
History of cardiac dysfunction including any of the following: