Age >= 18 years
Biopsy-proven relapsed or refractory lymphomas; relapsed is defined as a relapse that occurred after having a response to the last therapy that lasted > 6 months; refractory is no response or relapse within 6 months; previous biopsies < 6 months prior to treatment on this protocol will be acceptable
NOTE: Arms A/B - relapsed or refractory DLBCL within 24 months from the end of anthracycline-based therapy; no prior salvage therapy; patients can have received radiation therapy as part of initial treatment but not specifically for relapse
NOTE: Arm C patients include relapsed or refractory lymphoma patients of any type for which the recommended treatment includes one of the platinum-based regimens; of note, relapsed or refractory double-hit high grade lymphoma patients and relapsed or refractory Hodgkin lymphoma patients will be enrolled in Arm C; there is no limit on the number of prior therapies for Arm C patients; the patient must be eligible for a platinum-based regimen and must not have received the same regimen in the past without responding
Measurable or assessable disease: measurable disease is defined as measurable by computed tomography (CT) [dedicated CT or the CT portion of a positron emission tomography (PET)/CT] or magnetic resonance imaging (MRI): to be considered measurable, there must be at least one lesion that has a single diameter of >= 1.5 cm
Arms A/B - eligible for treatment with ifosfamide, carboplatin, and etoposide (+/- rituximab)
Arm C eligible for treatment with one of the following standard, every 3 week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):
Ifosfamide/carboplatin/etoposide (ICE) or rituximab/ifosfamide/carboplatin/etoposide (RICE);
Cisplatin, cytarabine (cytosine arabinoside), dexamethasone (DHAP) or RDHAP;
Gemcitabine hydrochloride (gemcitabine), dexamethasone, cisplatin (GDP) or rituximab, gemcitabine, dexamethasone, cisplatin (RGDP);
Gemcitabine and oxaliplatin (GemOx) or rituximab, gemcitabine and oxaliplatin (RGemOx);
Oxaliplatin, cytosine arabinoside, dexamethasone (OAD) or rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Hemoglobin >= 8.0 g/dL (may transfuse to meet this requirement), obtained =< 14 days prior to registration
Absolute neutrophil count (ANC) >= 1500/mm^3, obtained =< 14 days prior to registration
Platelet count >= 75000/mm^3, obtained =< 14 days prior to registration
Total bilirubin =< 2 x upper limit of normal (ULN) (if > 2 x ULN direct bilirubin is required and should be =< 1.5 x ULN), obtained =< 14 days prior to registration
Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement), obtained =< 14 days prior to registration
Creatinine =< 1.6 mg/dL; if over 1.6 then the calculated creatinine clearance must be >= 55 ml/min using the Cockcroft-Gault formula, obtained =< 7 days prior to registration
Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
Human immunodeficiency virus (HIV) test done =< 14 days prior to registration
Provide written informed consent
Willingness to have a central venous line [peripherally inserted central catheter (PICC) or PORT]
Willingness to provide mandatory blood specimens for correlative research
Willingness to provide mandatory tissue specimens for correlative research
Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Willingness to follow the requirements of the intravenous ascorbic acid program schedule
ARM D: Patients who had a diagnosis of CCUS with one or more TET2 mutations or TET2 mutations with concurrent splicing genes mutations (SRSF2, U2AF1, SF3B1, and ZRSR2) or epigenetic regulator mutations (DNMT3A, EZH2, IDH1, IDH2). CCUS diagnosis being defined based on the absence of definitive morphologic evidence of hematologic neoplasms from bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation with a variant allele frequency (VAF) of at least 2% using our institution's next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic)
ARM D: ECOG performance status (PS) 0, 1 or 2
ARM D: Patients must meet at least 1 of these 3 laboratory criteria to be enrolled:
Hemoglobin =< 10g/dL (obtained =< 7 days prior to registration)
Absolute neutrophil count (ANC) =< 1000/mm^3 (obtained =< 7 days prior to registration)
Platelet count =< 100,000/mm^ 3 (obtained =< 7 days prior to registration)
ARM D: Total bilirubin =< 2 x ULN (if > 2 x ULN direct bilirubin is required and should be =< 1.5 x ULN) (obtained =<7 days prior to registration)
ARM D: Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =<7 days prior to registration)
ARM D: Creatinine =< 1.6 mg/dL (obtained =<7 days prior to registration). If > 1.6, then the Calculated creatinine clearance must be >= 55 ml/min using the Cockcroft-Gault formula
ARM D: Negative pregnancy test, for persons of childbearing potential only (obtained =< 7 days prior to registration). NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
ARM D: Provide written informed consent
ARM D: Willingness to have a central venous line (PICC or PORT)
ARM D: Willingness to provide mandatory blood specimens for correlative research
ARM D: Willingness to return to enrolling institution (MCR) for follow-up (during the active monitoring phase of the study)
ARM D: Willingness to follow the requirements of the intravenous ascorbic acid program schedule
ARM E PRE-REGISTRATION: Age ≥ 18 years
ARM E PRE-REGISTRATION: New or an established diagnosis of 2016 World Health Organization (WHO) defined chronic myelomonocytic leukemia with a somatic TET2, IDH1, or IDH2 mutation requiring treatment with DNA methyltransferase inhibitors/hypomethylating agents
ARM E PRE-REGISTRATION: No prior CMML directed therapy.
Exception: Received ≤ 1 cycle of azacitidine, decitabine, erythropoiesis stimulating agent therapy (ESA), or oral decitabine and cedazuridine. NOTE: Prior exposure to hydroxyurea is allowed. Continuation beyond the first cycle must be discussed with the principal investigator (PI)
ARM E PRE-REGISTRATION: Creatinine ≤ 1.6 mg/dL. If > 1.6, then the Calculated creatinine clearance must be ≥ 55 ml/min using the Cockcroft-Gault formula
ARM E PRE-REGISTRATION: Willingness to provide mandatory research bone marrow sample for correlative research
ARM E PRE-REGISTRATION: ECOG performance status (PS) 0, 1, or 2
ARM E PRE-REGISTRATION: Provide written informed consent
ARM E REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
ARM E REGISTRATION: Willingness to return to enrolling institution (MCR) for follow-up (during the active monitoring phase of the study)
ARM E REGISTRATION: Recovered to grade 1 or baseline or established as sequelae from all toxic effects of previous therapy except alopecia
ARM E REGISTRATION: Absolute neutrophil count (ANC) ≥ 500/mm^3 (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Platelet count ≥ 20,000/mm^3 (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Total bilirubin ≤ 1.5 x ULN ( ≤ 3 x ULN for patients with Gilbert's syndrome) (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (obtained ≤ 7 days prior to registration)
ARM E REGISTRATION: Ability to complete questionnaire by themselves or with assistance
ARM E REGISTRATION: For a person of child-bearing potential (WOCBP): Must agree to use contraception or take measures to avoid pregnancy during the study. Adequate contraception is defined as follows:
ARM E REGISTRATION: WOCBP must have a negative serum or urine pregnancy test ≤ 7 days prior to registration. NOTE: WOCBP include any person who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea > 12 consecutive months); or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. Even women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an IUD or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), must be considered to be of child-bearing potential. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
ARM E REGISTRATION: Persons who are able to father a child must use contraception during the study and for 3 months after the last treatment dose.
ARM E REGISTRATION: Willingness to have a central venous line (PICC or PORT)
ARM E REGISTRATION: Willingness to follow the requirements of the intravenous ascorbic acid program schedule
Any of the following:
Any therapy =< 2 weeks prior to registration; NOTE: Exception: patients on ibrutinib or corticosteroids (any dose) may continue therapy up until the new regimen has started at investigator discretion; corticosteroids can be tapered to lowest possible dose after start of treatment at investigator discretion. Exception: Palliative radiation is allowed
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Receiving any other investigational agent which would be considered as a treatment for the lymphoma
Other active malignancy than lymphoma
NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer that could interfere with this protocol therapy; patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria; patients with non-melanotic skin cancer may enroll
History of myocardial infarction =< 6 months, or current symptomatic congestive heart failure or left ventricular ejection fraction (LVEF) < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
Patients with active central nervous system (CNS) lymphoma or active cerebrospinal fluid (CSF) involvement with malignant cells requiring CNS-specific therapy with IV or intrathecal (IT) methotrexate (MTX); Note: Patients with any prior CNS lymphoma (parenchymal or leptomeningeal) MUST be in complete remission (CR) in those compartments without any maintenance therapy required
Patients with uncontrolled or symptomatic kidney stones
Known paroxysmal nocturnal hemoglobinuria (PNH)
ARM D: Bona-fide hematological neoplasm
ARM D: Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
ARM D: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
ARM D: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
ARM D: History of myocardial infarction =< 6 months, or current symptomatic congestive heart failure or known LVEF < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
ARM D: Patients with uncontrolled or symptomatic kidney stones
ARM D: Known paroxysmal nocturnal hemoglobinuria (PNH)
ARM D: Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
ARM E PRE-REGISTRATION: Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes other than CMML
ARM E PRE-REGISTRATION: Active central nervous system disease
ARM E PRE-REGISTRATION: Any active disease condition that would render the protocol treatment dangerous or impair the ability of the patient to receive study drug
ARM E PRE-REGISTRATION: Concurrent active malignancy, except adequately treated nonmelanoma skin cancer. History of curatively treated in situ cancer of the cervix, curatively treated in situ cancer of the breast, or other solid tumors curatively treated is allowed as long as there is no evidence of disease for > 2 years
ARM E PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
ARM E PRE-REGISTRATION: Disease requiring systemic treatment with systemic immunosuppression with steroid steroids at a dose of ≥ 20 mg/day prednisone (or equivalent). Exceptions: Intermittent use of bronchodilators or inhaled steroids, local steroid injections, topical steroids
ARM E PRE-REGISTRATION: Patients with uncontrolled or symptomatic kidney stones
ARM E REGISTRATION: New York Heart Association (NYHA) class III/IV heart failure or active angina/angina equivalents
ARM E REGISTRATION: History of myocardial infarction ≤ 6 months, or current symptomatic congestive heart failure or known LVEF < 40% or with > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure
ARM E REGISTRATION: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, clinically significant cardiac arrhythmia, unstable angina pectoris, clinically significant nonhealing or healing wounds, pulmonary congestion or pulmonary edema, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection, clinical dehydration, or psychiatric illness/social situations that would limit compliance with study requirements
ARM E REGISTRATION: Known G6PD (glucose-6-phosphate dehydrogenase) deficiency (below lower limit of normal)
ARM E REGISTRATION: Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects: