1. Signed informed consent 2. Age ≥ 18 years and ≤ 65 years 3. Deemed eligible for allogeneic stem cell transplantation 4. Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor 5. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci
• A minimum genotypic identical match of 4/8 is required.
• The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 6. Subjects with adequate organ functions as measured by: 1. Cardiac: Left ventricular ejection fraction at rest must be ≥ 45% 2. Hepatic: Bilirubin ≤ 2.5 mg/dL and ALT, AST and Alkaline Phosphatase < 5 x ULN 3. Renal: Serum creatinine within normal range for age or creatinine clearance, or with a recommended GFR ≥ 50 mL/min/1.73m2 4. Pulmonary: FEV 1, FVC and DLCO (diffusion capacity) ≥ 50% predicted (corrected for hemoglobin); or O2 saturation > 92% on room air 7. Clinical diagnosis of one of the following: a. Acute Leukemia (includes T lymphoblastic lymphoma) in 2nd or subsequent complete remission (CR) i. Acute Lymphoblastic Leukemia (ALL) in 2nd or subsequent CR. ALL shall be morphologic remission at the time of transplant. Morphologic remission is defined that subjects with normal neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and no extramedullary disease ii. Acute Myeloid Leukemia (AML) in 2nd or subsequent CR with or without persistent minimal residual disease b. High-risk ALL in 1st CR (including features such as those in i-iii) i. Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements ii. Subjects over 30 years of age, or iii. Time to complete remission was greater than 4 weeks. c. High-risk AML in 1st CR (including features such as those listed in i-vii) i. Greater than 1 cycle of induction therapy required to achieve remission ii. Preceding myelodysplastic syndrome (MDS) iii. Presence of FLT3 abnormalities iv. FAB M6 or M7 leukemia v. Adverse cytogenetics for overall survival such as those associated with MDS vi. Complex karyotype (>3 abnormalities), or vii. Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(l1;19)(q23;p13.1) d. High risk Myelodysplastic Syndrome e. Non-Hodgkin's Lymphoma relapsed after autologous transplantation f. Non-Hodgkin's Lymphoma with insufficient autologous hematopoietic stem cells to undergo autologous transplantation g. CML i. in first chronic phase that has not attained at least a complete cytogenetic remission after exposure to at least 3 tyrosine kinase inhibitors ii. in accelerated phase that has not attained at least a complete cytogenetic remission iii. in second chronic phase 8. Performance status: Karnofsky score ≥60%. 9. Patient with hematologic malignancy not responding to /or not eligible for conventional therapy and are approved by Sponsor 1. HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate. 2. Autologous hematopoietic stem cell transplant < 3 months prior to enrollment. 3. Pregnancy or breast-feeding. 4. Evidence of HIV infection or known HIV positive serology. 5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). The treating physician will make final determination. 6. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma. 7. Prior allogeneic hematopoietic stem cell transplant. 8. Subjects with a history of primary idiopathic myelofibrosis. 9. Bovine product allergy.

• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment

1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML (i.e., with white blood cell [WBC] <13,000/microliter [mcL]) or low-blast acute myelogenous leukemia (AML). 2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
• Very high (>6 points).
• High (>4.5-6 points).
• Intermediate (>3-4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts. 3. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2. 4. Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers. Calculation of TRM score:
• 0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >=71 years).
• + 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).
• + 0 for (platelets <50), +1 for (platelets >=50). 1. Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug. 2. Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis. 3. Participants with AML with a WBC count >50,000/mcL. Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria. 4. Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:
• Age >75.
• Comorbidities.
• Inability to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM >=4).
• Physician decision (e.g., lack of available stem cell donor).
• The reason a participant is not eligible should be documented in the electronic case report form (eCRF). 5. Has either clinical evidence of or history of central nervous system involvement by AML. 6. Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia. 7. Is diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. 8. Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection. 9. Has prothrombin time (PT) or aPTT >1.5× upper limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment. 10. Has known human immunodeficiency virus (HIV) seropositive. 11. Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. 12. Has known hepatic cirrhosis or severe preexisting hepatic impairment. 13. Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension. 14. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.

• Pediatric participants 3 months to 17 years of age with clinically stable chronic renal anemia
• CKD with estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2 (determined by the Bedside Schwartz formula) or dialysis treatment for at least 8 weeks before the first dose of Mircera
• For participants on peritoneal dialysis (PD): a weekly Kt/V≥ 1.8
• For participants on HD: adequate HD, urea reduction ratio (URR) > 65% or Kt/V > 1.2 for participants on HD three times per week. Participants with fewer than or more than three HD sessions per week should have a weekly Kt/V≥ 3.6.
• Baseline Hb concentration 10.0-12.0 g/dL determined from the mean of two Hb values measured at Visit 1 (Week -3) and Visit 2 (Week -1)
• Stable SC maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa with the same dosing interval for at least 6 weeks before the first dose of Mircera
• Stable dose of epoetin alfa, epoetin beta, or darbepoetin alfa treatment with no weekly dose change > 25% (increase or decrease) for at least 4 weeks before the first dose of Mircera
• Adequate iron status defined as ferritin≥100 ng/mL or transferrin saturation (TSAT)≥ 20% (or percentage of hypochromic red cells < 10%); mean of two values measured during screening.
• Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period
• RBC transfusions within 8 weeks before screening or during the screening period
• Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types) Hemolytic anemia, Active malignant disease
• PD subjects with an episode of peritonitis within the past 30 days prior to screening and/or during the screening period
• Uncontrolled or symptomatic inflammatory disease (e.g., systemic lupus erythematosus)
• Uncontrolled hypertension as assessed by the investigator
• Epileptic seizures within 3 months prior to screening and during the screening period
• Administration of any investigational drug within 4 weeks prior to screening or planned during the study
• Severe hyperparathyroidism (intact parathyroid hormone [PTH]≥ 1000 pg/mL or whole PTH≥ 500 pg/mL) or biopsy-proven bone marrow fibrosis
• Kidney transplant with use of immunosuppressive therapies known to exacerbate anemia
• Known hypersensitivity to recombinant human erythropoietin (EPO), polyethylene glycol, or any constituent of the study drug formulation
• Anti-EPO antibody (AEAB)-mediated pure red cell aplasia (PRCA) or history of AEAB mediated PRCA or positive AEAB test result in the absence of PRCA
• High likelihood of early withdrawal or interruption of the study (e.g., planned living donor kidney transplant within 5 months of study start)
• Planned elective surgery during the entire study period

• Patients must be newly diagnosed with de novo acute myelogenous leukemia
• Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
• Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
• Patients with < 20% bone marrow blasts are eligible if they have:
• A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities
• The unequivocal presence of megakaryoblasts, or
• Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
• Patients with any performance status are eligible for enrollment
• Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy; patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
• Patients with any of the following constitutional conditions are not eligible:
• Fanconi anemia
• Shwachman syndrome
• Any other known bone marrow failure syndrome
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
• Patients with any of the following oncologic diagnoses are not eligible:
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia (JMML)
• Philadelphia chromosome positive AML
• Biphenotypic or bilineal acute leukemia
• Acute promyelocytic leukemia
• Acute myeloid leukemia arising from myelodysplasia
• Therapy-related myeloid neoplasms Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
• Pregnancy and breast feeding
• Female patients who are pregnant are ineligible
• Lactating females are not eligible unless they have agreed not to breastfeed their infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

• Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization [FISH]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:
• Patients must have measurable disease that has not been previously irradiated, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional imaging or >= 10 mm with spiral computed tomography (CT) scan; if the patient has been previously irradiated, there must be evidence of progression since the radiation
• Please note, this trial includes mandatory tumor biopsies pre-treatment, during cycle 1 and at the time of disease progression of accessible tumor; having accessible tumor for biopsy is not required for eligibility; we expect that at least 80% of patients will have accessible tumor for these biopsies, however
• Prior therapy
• Please note, the washout period for prior therapies cannot be shortened
• Please note, prior therapies can be from any time in the past
• ALK+ ALCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen including an anthracycline, if not contraindicated, and prior brentuximab; prior crizotinib or other ALK inhibitor therapy, while recommended, is not mandatory; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• MCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen and prior ibrutinib or other BTK inhibitor therapy; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• BCL6+ DLBCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included an anthracycline, if not contraindicated; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 months
• Absolute neutrophil count >= 1,000/mcL
• Platelets >= 75,000/mcL, unless due to marrow involvement by lymphoma in which case a platelet count of >= 30,000/mcL will be used
• Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome or hemolysis, in which case =< 3.0 x ULN is allowed
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal
• Creatinine =< 1.5 x ULN or a creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Potassium above the institutional lower limit of normal (supplementation to meet this is allowed)
• Magnesium above the institutional lower limit of normal (supplementation to meet this is allowed)
• Human immunodeficiency virus (HIV)+ patients are eligible for the trial provided they meet the other study criteria in addition to the following:
• CD4+ T-cells >= 250/mm^3
• HIV sensitive to antiretroviral therapy
• Zidovudine not allowed
• Long term survival anticipated on the basis of HIV alone were it not for the lymphoma
• No concurrent acquired immunodeficiency syndrome (AIDS)-defining illness other than the lymphoma
• The effects of AT13387 (onalespib) on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after the completion of AT13387 (onalespib) administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of AT13387 (onalespib) administration
• Although the pharmacokinetic (PK) data in humans is still unknown, the potential for drug-interaction cannot be ruled out; pre-clinical studies suggest that AT13387 (onalespib) is a substrate of P-glycoprotein (P-gp), a moderate inhibitor of BCRP and P-gp, and a strong inhibitor of MATE 1/2-K; patients must be willing to not take St. John wort or grapefruit juice while participating in this trial and should avoid drugs that are strong inducers of P-gp, and to switch to alternative drugs when available
• Hepatitis B positive patients are eligible; prophylactic hepatitis B virus (HBV) therapy is recommended but only if there is no circulating virus detectible
• Transformed lymphoma patients are eligible
• Ability to understand and the willingness to sign a written informed consent document
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; steroids for symptom palliation are allowed, but must be either discontinued or on stable doses at the time of initiation of protocol therapy
• Patients who are receiving any other investigational agents; all investigational agents other than ibrutinib must have been discontinued at least 4 weeks prior to beginning treatment; prior ibrutinib therapy must have been discontinued at least 2 weeks prior to beginning therapy
• Patients with known leptomeningeal or brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AT13387 (onalespib)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• There will be no exclusion of patients with known visual impairment or symptoms, including by not limited to peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; patients will have a baseline ophthalmologic exam to serve as a point of comparison and further exams as needed should visual symptoms develop; no pretreatment eye exam findings or ocular symptoms have been associated with an increased risk of ocular toxicity seen with AT13387
• Pregnant women are excluded from this study because AT13387 (onalespib) has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AT13387 (onalespib), breastfeeding should be discontinued if the mother is treated with AT13387 (onalespib)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years; patients with prostate cancer are allowed if prostate specific antigen (PSA) is less than 1
• Patients should not receive immunization with attenuated live vaccine within one week of study entry or during study period
• History of noncompliance to medical regimens
• Consistent corrected QT (QTc) > 450 msec for men and > 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs)
• Left ventricular ejection fraction (LVEF) < 50%, regardless of whether there are symptoms of heart failure

• Patients must have a histopathologically confirmed diagnosis of an aggressive B-cell non-Hodgkin lymphoma that is recurrent or refractory to standard therapy
• For the purpose of this study, aggressive B-cell NHL will be deemed any lymphoma belonging to one of the following groups according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms
• For the purposes of stratification, diagnoses are grouped into 2 categories:
• Category A
• Burkitt lymphoma
• Burkitt-like lymphoma with 11q aberration
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
• High-grade B-cell lymphoma, not otherwise specified (NOS)
• Category B
• Diffuse large B-cell lymphoma (DLBCL), NOS
• Diffuse large B-cell lymphoma (DLBCL), NOS; germinal center B-cell type
• Diffuse large B-cell lymphoma (DLBCL), NOS; activated B-cell type
• Large B-cell lymphoma with IRF4 rearrangement
• T-cell/histiocyte-rich large B-cell lymphoma
• Primary DLBCL of the central nervous system (CNS)
• Primary cutaneous DLBCL, leg type
• Epstein-Barr virus (EBV)+ DLBCL, NOS
• EBV+ mucocutaneous ulcer
• DLBCL associated with chronic inflammation
• Lymphomatoid granulomatosis
• Primary mediastinal (thymic) large B-cell lymphoma
• Intravascular large B-cell lymphoma
• ALK+ large B-cell lymphoma
• Plasmablastic lymphoma
• Primary effusion lymphoma
• Human herpesvirus (HHV)-8+ DLBCL, NOS
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
• Patients must have measurable disease, defined as at least one lesion that is > 15 mm (1.5 cm) in the longest axis on cross-sectional imaging and measurable in two perpendicular dimensions per computed tomography (spiral computed tomography [CT]), positron emission tomography (PET)-CT or magnetic resonance imaging (MRI)
• Patients must have disease that has relapsed after or is refractory to at least 2 lines of standard therapy; the remaining standard treatment options are unlikely to be effective in the opinion of the treating physician, or patient is felt to be ineligible for such therapies or the patient refuses such therapies; patients who have undergone autologous stem cell transplant are eligible as long as they meet all other criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of greater than 12 weeks
• White blood cell (WBC) >= 2000/mm^3 (within 14 days of registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 14 days of registration)
• Platelet count >= 100,000/mm^3 (within 14 days of registration)
• Hemoglobin > 9.0 g/dL (within 14 days of registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 14 days of registration)
• Aspartate transaminase (aspartate aminotransferase [AST]) =< 2.5 x ULN (within 14 days of registration)
• Calculated creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula) (within 14 days of registration)
• Females of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
• Ability to understand and the willingness to sign a written informed consent document
• Patient has received chemotherapy, targeted agent, or radiotherapy within 4 weeks or at least 5 half-lives, whichever is longer, prior to registration
• Palliative (limited-field) radiation therapy is permitted, if all of the following criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Patient has received immunotherapy (including monoclonal antibodies) within 4 weeks prior to registration
• Patients who have not recovered to grade 1 or less from any adverse events due to agents administered more than 4 weeks earlier (excluding alopecia)
• Patients who are receiving any other investigational agents
• Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients who have received autologous stem cell transplant (ASCT) =< 12 weeks prior to the first dose of study drug
• Patients with a prior history of allogeneic stem cell or solid organ transplantation
• Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI obtained within 4 weeks of registration or progressive neurological decline
• Patients with primary CNS lymphoma who develop systemic recurrence following standard therapy may be included as long as no active CNS disease is present at the time or enrollment; similarly, patients with secondary involvement of the CNS from a systemic lymphoma may be included as long as the CNS disease has been optimally treated and they demonstrate no evidence of active CNS disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1127 (varlilumab) and/or nivolumab
• History of severe hypersensitivity reaction to any monoclonal antibody
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because CDX-1127 (varlilumab) and nivolumab are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CDX-1127 (varlilumab) or nivolumab, breastfeeding should be discontinued if the mother is treated with CDX-1127 (varlilumab) or nivolumab
• Patients with human immunodeficiency virus (HIV) are eligible for the study provided they meet the other protocol criteria in addition to the following:
• Undetectable HIV load by standard polymerase chain reaction (PCR) clinical assay within 60 days prior to registration
• Absolute CD4 count of >= 200 mm^3 within 60 days prior to registration
• Willing to maintain adherence to combination antiretroviral therapy
• No history of acquired immunodeficiency syndrome (AIDS) defining condition (other than lymphoma or CD4 cell count < 200 mm^3)
• Likely to have near normal lifespan if not for the presence of relapsed/refractory lymphoma
• Patients with evidence of hepatitis B virus (HBV) are eligible provided there is minimal hepatic injury and the patient has undetectable HBV on suppressive HBV therapy; patient must be willing to maintain adherence to HBV therapy
• Patients with previously treated and eradicated hepatitis C virus (HCV) who have minimal hepatic injury are eligible
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
• Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
• Patients with other active malignancy =< 3 years prior to registration for which active treatment is required must be excluded; patients with composite lymphomas that have a non-B-cell component must be excluded EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix

• Stratum I
• Patients must be less than 18 years of age at the time of diagnosis.
• Patients must have histological verification of the diagnosis of Langerhans cell histiocytosis according to the criteria described in Section 6.1
• Signed informed consent form
• Stratum II
• Patients of Stratum I who have:
• Progressive disease (AD worse) in non-risk organs after 6 weeks (Initial Course
• AD intermediate or worse in non-risk organs or AD better in risk organs after 12 weeks (Initial Course 2)
• Disease progression (AD worse) in non-risk organs at any time during continuation treatment
• Active disease at the end of Stratum I treatment
• Disease reactivation in non-risk organs at any time after completion of Stratum I treatment
• Stratum III
• Patients from Stratum I who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2).
• Presence of unequivocally severe organ dysfunction at the above mentioned evaluation points (hematological dysfunction, liver dysfunction, or both of them) as
• Hb <70 g/L (<7.0 g/dl) and/or transfusion dependency
• PLT <20 x109/L (20,000/μL) and/or transfusion dependency (both criteria have to be fulfilled) AND/OR
• Liver dysfunction (or digestive involvement with protein loss)
• Total protein <55 g/L or substitution dependency
• Albumin <25 g/L or substitution dependency (at least one of the two criteria to be fulfilled)
• Stratum IV
• Patients from Stratum I or Stratum III who fulfill the following criteria:
• AD worse in risk organs after week 6 (after Initial Course 1), or AD worse or AD intermediate in risk organs after week 12 (after Initial Course 2) of Stratum I OR
• AD worse after the 2nd and 3rd 2-CdA/Ara-C course, and those AD worse or AD intermediate after the 4th 2-CdA/Ara-C course of Stratum III AND
• 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).
• Informed consent: All patients or their legal guardians (if the patient is <18 years of age) must sign an Ethics or institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. When appropriate, younger patients will be included in all discussions in order to obtain assent.
• Adequate organ function: Patients should have adequate hepatic, renal, cardiac and pulmonary function to undergo reduced intensity HCT based upon local institutional guidelines, or at a minimum meet requirements noted in eligibility checklist Appendix A-VIII_1. However, significant hepatic and pulmonary dysfunction, if secondary to underlying LCH disease activity, will not exclude patients from protocol enrollment and should be discussed with the National PI Coordinator and the Coordinating Principal Investigator.
• Stratum V
• All patients with verified diagnosis of LCH and MRI findings consistent with ND-CNSLCH irrespective of previous treatments (also those not registered to other Strata ofLCH-IV).
• Patients with isolated tumorous CNS-LCH (including isolated DI with mass lesion in the hypothalamus-pituitary axis). In patients with already established diagnosis of LCH and radiologic finding of CNS lesions compatible with LCH, a biopsy of the lesion is not obligatory. In all other cases a biopsy of the lesion is needed for inclusion into the study
• Stratum VI -- Patients with newly diagnosed SS-LCH and localization other than "multifocal bone",isolated tumorous CNS lesion, or isolated "CNS-risk" lesion.
• Stratum VII -- All patients registered in LCH IV (regardless of treatment) as long as consent for longterm follow-up has not been withheld.
• Stratum I
• Pregnancy (patients of child-bearing age must be appropriately tested before chemotherapy)
• LCH-related permanent consequences (e.g. vertebra plana, sclerosing cholangitis, lung fibrosis, etc.) in the absence of active disease
• Prior systemic therapy
• Stratum II
• Patients with progressive disease in risk organs
• Permanent consequences (e.g. sclerosing cholangitis, lung fibrosis, etc.) without evidence of active LCH in the same organ or in any other locations
• No written consent of the patient or his/her parents or legal guardian
• Stratum III
• The presence of any of the following criteria will exclude the patient from the study:
• Isolated sclerosing cholangitis without evidence of active hepatic LCH as the only evidence of risk organ involvement.
• Inadequate renal function as defined by serum creatinine > 3x normal for age
• Stratum IV
• Pulmonary failure (requiring mechanical ventilation) not due to active LCH.
• Isolated liver sclerosis or pulmonary fibrosis, without active LCH.
• Uncontrolled active life-threatening infection.
• Decreased renal function with a GFR of less than 50ml/1.73m2/min.
• Pregnancy or active breast feeding
• Failure to provide signed informed consent
• Stratum VI
• Patients with SS-LCH who have an isolated tumorous CNS lesion (they are eligible for Stratum V),
• Patients with isolated "CNS-risk" or multifocal bone lesions (they are eligible for Stratum I, Group 2)

• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5%
•25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.

1. Voluntarily signed consent; 2. Age of ≥ 18 and ≤ 80 years; 3. Received sufficient prior lines of myeloma therapy; 4. Received treatment with at least one proteasome inhibitor, one IMiD and daratumumab. 5. The patients should have measurable disease per IMWG definition. 6. Estimated life expectancy > 12 weeks; 7. ECOG performance score 0-1; 8. Patients should have reasonable CBC counts, renal and hepatic functions; 9. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis; 10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 6 months after T cell infusion; 11. Men must be willing to use effective and reliable method of contraception for at least 6 months after T cell infusion. 1. Pregnant or lactating women; 2. HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection; 3. Any uncontrolled active infection; 4. AEs from previous treatment that have not recovered; 5. Patients who have had anti-BCMA therapy; 6. Patients who have graft versus host disease (GvHD); 7. Patients have received stem cell transplantation less than 12 weeks before leukapheresis; 8. Patients have received any anti-cancer treatment before leukapheresis; 9. Patients have received steroids before leukapheresis or lymphodepletion; 10. Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage; 11. Patients have been administered live attenuated vaccine before leukapheresis or lymphodepletion; 12. Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or CT053 CAR BCMA T cell; 13. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients; 14. Patients have clinical significant pulmonary conditions; 15. Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy; 16. Patients with second malignancies in addition to MM are not eligible; 17. Patients have central nervous system (CNS) metastases or CNS involvement; 18. Patients have significant neurologic disorders; 19. Patients are unable or unwilling to comply with the requirements of clinical trial; 20. Patients have received major surgery prior to leukapheresis or prior to lymphodepletion.

1. Signed informed consent. Consent must be obtained prior to any study-related procedure. 2. Age ≥ 18 years 3. Histologically confirmed AML or MDS: 1. AML
•relapsed or refractory AML and refuses or is not a candidate for intensive chemotherapy (due to prior failure or not eligible due to expected intolerance) or allogeneic transplant 2. MDS
•relapsed or refractory MDS with > 5% blasts in the marrow or any blasts in the peripheral blood. Patients must have failed prior treatment with an HMA (azacitidine, decitabine, or other HMA agent); failure is defined as intolerance to HMA, lack of response [no complete remission (CR) by at least 6 cycles], or have IWG-defined progressive disease during or after treatment with an HMA. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 5. Life expectancy of > 2 months in the Investigator's opinion 6. White blood cells (WBC) ≤ 25,000 cells/mm3 (may receive hydroxyurea to bring WBC count down prior to and during the first cycle of treatment with study drug if necessary) 7. Creatinine ≤ 2 × upper limit of normal (ULN) 8. Adequate liver test parameters: total bilirubin < 2.5 × ULN (if disease related or secondary to Gilbert's disease, then total bilirubin < 3.5 mg/dL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) < 3 × ULN 9. Prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 × ULN 10. Patients and partners of childbearing potential must be willing to use adequate contraception during the study and for 2 months after last study drug administration. Adequate contraception means less than 1% chance of pregnancy may occur with proper use of the method(s). 1. Any central nervous system (CNS) (cerebral/meningeal) disease related to underlying malignancy 2. History of seizures 3. Acute promyelocytic leukemia 4. Prior anti-CD123 therapy outside of this study 5. Any clinically significant graft-versus-host disease (GVHD) secondary to prior allogenic transplant. Patients must be >90 days from transplant and have been on no immunosuppressive therapy for >30 days. Topical corticosteroids for minor skin rash (<5% body surface area) is acceptable. Prior solid organ transplant is acceptable provided the patient is on no immunosuppressive therapy. 6. Any therapy or experimental treatment for MDS or AML within 7 days of the first dose of study drug. Must have recovered to Grade ≤ 1 from any Grade 2 to 4 toxicity from previous treatment. The use of hydroxyurea is acceptable and does not exclude the patient. 7. Active, uncontrolled infection requiring systemic therapy. If the infection is controlled or has resolved, maintenance and/or prophylactic systemic antimicrobials are permitted. 8. Major surgery within 3 weeks prior to first dose of study drug 9. Known to be positive for HIV, hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) 10. Pregnant or breast feeding 11. Any other active systemic malignancies. Exceptions: noninvasive non-melanoma skin cancer, in situ carcinoma, cervical intraepithelial neoplasia, and breast or prostate cancer that is well controlled with anti-hormonal therapy 12. Any current autoimmune disorder requiring immunosuppressive therapy 13. Requires more than a replacement dose of corticosteroids (i.e., > 10 mg/day of prednisone or equivalent) 14. Any uncontrolled medical condition, including but not limited to: 1. Symptomatic congestive heart failure ≥ Class III (New York Heart Association Functional Classification) 2. Uncontrolled hypertension 3. Unstable angina 4. Myocardial infarction within previous 6 months 5. Clinically significant arrhythmias not controlled by medication 6. Uncontrolled metabolic disorders such as hypercalcemia 15. Substance use disorder, psychiatric, cognitive, or any other condition that, in the opinion of the Investigator, would pose a risk to the patient's safety, may compromise the patient's ability to understand and comply with the protocol or provide informed consent, or interfere with the study evaluation 16. Any difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration, or may cause a safety concern for the patient

• All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures). Risk stratification will not be possible without the submission of viable samples. Given there are multiple required samples, bone marrow acquisition techniques such as frequent repositioning or performing bilateral bone marrow testing should be considered to avoid insufficient material for required studies. Consider a repeat marrow prior to starting treatment if there is insufficient diagnostic material for the required studies
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
• Patient must have 1 of the following:
• >= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
• In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
• < 20% bone marrow blasts with one or more of the genetic abnormalities (sample obtained within 14 days prior to enrollment)
• A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
• ARM C: Patient must be >= 2 years of age at the time of Late Callback
• ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
• ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
• ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
• ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
• ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
• ARM D: Patient must be >= 2 years of age at the time of Late Callback
• ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
• ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
• ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
• ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
• NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
• NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
• NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
• NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
• NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
• Patients with myeloid neoplasms with germline predisposition are not eligible
• Fanconi anemia
• Shwachman Diamond syndrome
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
• Any other known bone marrow failure syndrome
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia (JMML)
• Philadelphia chromosome positive AML
• Mixed phenotype acute leukemia
• Acute promyelocytic leukemia
• Acute myeloid leukemia arising from myelodysplasia
• Therapy-related myeloid neoplasms
• Administration of prior anti-cancer therapy except as outlined below:
• Hydroxyurea
• All-trans retinoic acid (ATRA)
• Corticosteroids (any route)
• Intrathecal therapy given at diagnosis
• In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
• ARM D: Patients with congenital long QT syndrome or congenital heart block are not eligible for this treatment arm

• Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
• Age ≥ 18 years
• Life expectancy > 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed diagnosis of one of the following, in accordance with WHO diagnostic criteria:
• Escalation:
• Diffuse Large B-cell Lymphoma (DLBCL, including primary mediastinal large B cell lymphoma, T cell rich B cell lymphoma, and high-grade B cell lymphoma NOS). Patients with Burkitt's, lymphoblastic lymphoma, follicular lymphoma, and mantle cell lymphoma are not included. OR
• Acute Myeloid Leukemia (AML)
• Expansion:
• Diffuse Large B-cell Lymphoma and acute myeloid leukemia as above.
• VEN Refractory expansion cohort (Diffuse Large B-cell Lymphoma and acute myeloid leukemia only): Patients must have previously received and failed venetoclax therapy (either monotherapy or combination) during their treatment course (i.e., patients may receive non-VEN therapy immediately prior to enrollment on this study). Treatment failure is defined as evidence of disease progression after ≥ 1 cycle (four weeks) of full-intensity venetoclax-based therapy (i.e., 28 days exclusive of ramp-up. Patients that require dose reductions due to intolerance may be considered for this cohort after discussion with the sponsor.)
• Relapsed or refractory following ≥ 1 line(s) of prior therapy
• Patients that relapse ≥ 3 months after allogeneic hematopoietic cell transplantation (HCT) are eligible.
• Female patients of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
• For leukemia and DLBCL with known or suspected marrow involvement, patients must have at least 10-15 mL of bone marrow aspirate material obtained within 14 days of beginning treatment on this study. Patients with DLBCL must have 3-5 unstained slides, or tissue block, available for evaluation within 14 days of study enrollment in the expansion cohorts. DLBCL patients enrolled during the escalation phase must have blocks available for submission within 28 days of beginning treatment.
• CBC testing must confirm adequate marrow reserve, as demonstrated by:
• DLBCL: Hgb ≥ 10g/dL, platelets ≥ 75,000 cells/mm3 , ANC ≥ 1,000 cells/mm3
• Adequate organ function, as demonstrated by:
• Total bilirubin < 1.5 x upper limit of normal (ULN) (except patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia), who must have a total bilirubin of < 3 x ULN, and
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 x ULN
• Calculated creatinine clearance > 50 mL/min (per the Cockcroft-Gault formula).
• Patients with laboratory evidence of liver or kidney dysfunction secondary to underlying disease, that is expected to reverse with treatment, may be enrolled after discussion with the sponsor/investigator.
• Patients who are pregnant or lactating
• Patients who received any systemic anticancer therapy including investigational agents or radiation ≤3 weeks (or ≤5 half-lives of the drug [whichever is shorter]) prior to C1D1. Hydroxyurea is permitted for up to 14 days in AML patients
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy. With the exception of alopecia or fatigue, patients must have recovered to baseline or ≤ Grade 1 (NCI-CTCAE v4.03) residual toxicity prior to first dose of protocol-indicated treatment.
• Participation in another clinical trial with any investigational drug within 14 days prior to study enrollment.
• Patients included in the VEN refractory cohort that have discontinued venetoclax therapy (either monotherapy or combination) due to toxicity or hypersensitivity, including prior history of grade 3/4 TLS during prior VEN exposure
• In dose expansion cohorts, except venetoclax refractory cohort, no prior treatment with SINE compounds, another XPO1 inhibitor, or BCL-2 inhibitors.
• Active GVHD requiring calcineurin inhibitors or steroid dosing ≥ 10mg/day prednisone (or equivalent) or < 3 months from allogenic hematopoietic cell transplant (HCT).
• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral.
• Major surgery within 2 weeks of first dose of study drug.
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety.
• Unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia therapy are excluded; 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded), or
• Congestive heart failure (CHF) of NYHA Class ≥3, or
• Myocardial infarction (MI) within 3 months.
• Known active Hepatitis B or Hepatitis C infection (Hepatitis testing is not required as part of this study).
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study).
• Subject has received the following ≤ 7 days prior to Cycle 1, Day 1: Strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
• Subject has received the following ≤ 5 days prior to Cycle 1, Day 1: Strong and moderate CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit ≤ 3 days prior to Cycle 1, Day 1.
• Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disease, disorder, syndrome, or dysfunction that could significantly affect the absorption of oral study drug
•e.g. Crohn's disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption syndrome, or bowel obstruction.
• Inability or unwillingness to take required and recommended medications intended to prevent and treat potential adverse events of tumor lysis syndrome (TLS), nausea and vomiting, loss of appetite, and fatigue.
• Patients unwilling to comply with the protocol

Pre-operative: 1. Less than 18 years of age. 2. Requires an elective (non-emergent), open (non-laparoscopic), pelvic, abdominal, or thoracic (non-cardiac) surgical procedure. 3. Subject and/or subject's legal guardian is willing to give permission for the subject to participate in the clinical trial and provide written informed consent for the subject. In addition, assent must be obtained from pediatric subjects who possess the intellectual and emotional ability to comprehend the concepts involved in the clinical trial. Intra-operative: 4. Presence of an appropriate (as defined in inclusion criterion 5) parenchymous or soft tissue TBS identified intra-operatively by the investigator (the surgeon). 5. TBS has Grade 1 (mild) or Grade 2 (moderate) bleeding intensity according to the investigator's (the surgeon's) judgment. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale. Pre-operative: 1. Admitted for trauma surgery. 2. Unwilling to receive blood products. 3. Known history of severe (eg, anaphylactic) reaction to blood products. 4. Known history of intolerance to any of the components of the investigational product (IP). 5. Female subjects who are pregnant, breastfeeding or, if of child-bearing potential (ie, adolescent), unwilling to practice a highly effective method of contraception. 6. Previously enrolled in a clinical trial with FS Grifols. 7. Currently participating, or during the study is planned to participate, in any other investigational device or medicinal product study without prior and explicit approval from the sponsor. Intra-operative: 8. An appropriate parenchymous or soft tissue TBS (as defined in exclusion criteria 9 and 10) cannot be identified intra-operatively by the investigator (the surgeon). 9. TBS has Grade 3 (severe) bleeding according to the investigator's (the surgeon's) judgment that cannot be controlled with conventional surgical techniques to Grade 1 or Grade 2 bleeding. The intensity of the bleeding at the TBS will be rated by the investigator using the 5-point validated bleeding severity scale. 10. TBS is in an actively infected surgical field. 11. Occurrence of major intra-operative complications that require resuscitation or deviation from the planned surgical procedure. 12. Application of any topical hemostatic agent on the resection surface of parenchyma or soft tissue prior to application of the IP.

Subjects must satisfy all of the following criteria to be enrolled in the study: 1. Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy 2. Subject is ≥ 18 years of age at the time of initial diagnosis of MM 3. Subject has measurable disease at initial diagnosis by
• M-protein and/or
• Light chain MM without measurable disease in the serum or urine 4. Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:
• ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
• ISS Stage III and serum LDH > ULN 5. Subject has Eastern Cooperative Oncology Group performance ≤ 1 6. Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment:
• Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
• Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone) The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment: At initial diagnosis, screening and prior to initiation of induction therapy for MM: 1. Subject has non-secretory MM During Screening: 2. Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol 3. Subject has any of the following laboratory abnormalities: 1. Absolute neutrophil count < 1,000/μL 2. Platelet count < 50,000 mm3 3. Hemoglobin < 8 g/dL (< 4.9 mmol/L) 4. Serum creatinine clearance < 45 mL/min 5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) 6. Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal 7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome 8. INR or aPTT > 1.5 × ULN 4. Subject has history or presence of clinically significant CNS pathology 5. Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy 6. Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen 7. Subjects has moderate or severe pulmonary hypertension 8. Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug 9. Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening 10. Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment 11. Subject has cardiac conditions such as: 1. Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45% 2. Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities 12. Subject has Pulmonary conditions such as: 1. Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal. 2. Inadequate pulmonary function defined as oxygen saturation < 92 % on room air 13. Subject needs ongoing treatment with chronic immunosuppressants 14. Subject has history of primary immunodeficiency 15. Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C

Key
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Individual cases of patients with ECOG 2 performance status, whose ECOG status is expected to improve as a consequence of effective therapy, may be discussed with the medical monitor for potential enrollment
• Patients must have symptomatic myeloma at the time of study entry with myeloma-related organ damage or tissue dysfunction (such as hypercalcemia, renal insufficiency, bone lytic lesions, or anemia)
• Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chain (FLC)
• Measurable disease is defined as 1 or more of the following: 1. Serum M-protein ≥1 g/dL, 2. Urine M-protein ≥200 mg/24-hour, and/or 3. FLC assay with involved FLC level ≥10 mg/dL with an abnormal serum FLC ratio
• A patient with Immunoglobulin A (IgA) myeloma but without measurable M-protein may be enrolled if quantitative IgA levels are elevated and can be followed longitudinally
• A patient with non-secretory MM may be considered for enrollment after discussion with the sponsor that includes the feasibility of an individualized plan for response assessment
• Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease, or intolerance or refusal of the therapy, and including either: 1. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody, OR 2. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor. Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
• Adequate hematologic function as measured by: 1. Platelet count > 50 x 109/L. A patient may not have received a platelet transfusion within 7 days in order to meet this platelet eligibility requirement. 2. ANC > 1.0 x 109/L. A patient may not have received granulocyte colony stimulating factor (G-CSF) within 2 days in order to meet this absolute neutrophil count eligibility requirement. 3. Hemoglobin > 8.0 g/dL
• Adequate hepatic function, defined as: 1. Total bilirubin ≤1.5 x ULN 2. Transaminase (ALT, AST) ≤2.5 x ULN 3. Alkaline phosphatase ≤2.5 x ULN
• Patients with Gilbert syndrome do not need to meet this total bilirubin requirement provided that the total bilirubin is unchanged from the baseline value. d. Serum creatinine clearance by Cockcroft-Gault >30 mL/min
• A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility criteria may be considered for enrollment if a measured creatinine clearance (based on 24-hour urine collection or other reliable method) is >30 mL/min
• Life expectancy of at least 6 months Key
• Patients with known MM brain lesions or meningeal involvement with MM (suspected central nervous system (CNS) myeloma should be excluded by radiographic imaging and/or lumbar puncture, as appropriate)
• History of neurodegenerative condition or CNS movement disorder
• Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)
• Prior treatment with any anti-BCMA antibody (including antibody-drug conjugate or bispecific antibody) or BCMA-directed CAR T therapy
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; or other uncontrolled infection 1. Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/microliter either spontaneously or on a stable antiviral regimen) are permitted. 2. Patients with hepatitis B (Hepatitis B Surface Antigen Test positive [HepBsAg+]) who have controlled infection (serum HBV DNA polymerase chain reaction [PCR] that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. 3. Patients who are HCV antibody-positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
• History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment NOTE: Other protocol defined Inclusion/Exclusion Criteria apply.

• Confirmed diagnosis of multiple myeloma as defined by the International Myeloma Working Group (IMWG) criteria.
• Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and must have documented disease progression during or after their most recent therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Must have at least 1 aspect of measurable disease, defined as one of the following; 1. Urine M-protein excretion >=200 mg per 24-hour, or 2. Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or 3. Serum free light chain (FLC) assay: involved FLC level >=10 mg per dL (>=100 mg per liter) and an abnormal serum free light chain ratio (<0.26 or >1.65).
• All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be <=Grade 1 at the time of enrollment, except for alopecia.
• Adequate organ function
• Intolerant to daratumumab.
• Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive disease during treatment with anti-CD38 therapy, or within 60 days of completing that treatment).
• Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease during treatment with a bortezomib-containing regimen of 1.3 mg/m^2 twice weekly, or within 60 days of completing that treatment). Note: participants with progressive disease during treatment with a weekly bortezomib regimen are allowed.
• Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.
• Prior treatment with anti-B-cell maturation antigen (anti-BCMA) therapy.
• Prior allogenic stem cell transplant.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions, including renal, liver, cardiovascular, or certain prior malignancies.
• Corneal epithelial disease.

DISEASE CHARACTERISTICS:
• Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
• Patients must have at least one objective measurable disease parameter
• Abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
• Measurable disease in the liver is required if the liver is the only site of lymphoma
• Patient must have no CNS involvement PATIENT CHARACTERISTICS:
• ECOG performance status 0-2
• ANC ≥ 1,500/mcL (1.5 x 10^9/L)*
• Platelets ≥ 100,000/mcL (100 x 10^9/L)* NOTE: *Unless due to marrow involvement.
• AST/ALT ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN
• Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
• Women (sexually mature female) must not be pregnant or breast-feeding
• Negative pregnancy test
• Women of childbearing potential and sexually active males use an accepted and effective method of contraception
• Men must agree to use a latex condom during sexual contact with a female of child-bearing potential, even if they have had a successful vasectomy
• All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
• No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, or any surgically or radiation-cured malignancy continuously disease free for ≥ 5 years so as not to interfere with interpretation of radiographic response
• Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they must register into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
• Patients must have no medical contra-indications to, and be willing to take, deep vein thrombosis (DVT) prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have DVT prophylaxis
• Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have therapeutic doses of low-molecular weight heparin or warfarin to maintain an INR between 2.0
•3.0
• Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis
• Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment
• Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment
• Males must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment
• HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:
• HIV is sensitive to antiretroviral therapy
• Must be willing to take effective antiretroviral therapy, if indicated
• No history of CD4 prior to or at the time of lymphoma diagnosis < 300 cells/mm³
• No history of AIDS-defining conditions
• If on antiretroviral therapy, must not be taking zidovudine or stavudine
• Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later
• Patients must not have grade 2 or greater peripheral neuropathy
• Patients must not have NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
• Patients must not have hypersensitivity to bortezomib, boron, or mannitol
• Patients must not have a serious medical or psychiatric illness likely to interfere with study participation PRIOR CONCURRENT THERAPY:
• No prior therapy for MCL, except < 1 week of steroid therapy for symptom control
• HIV-positive patients are not excluded, but to enroll, must meet all of the below criteria:
• Must be willing to take effective antiretroviral therapy if indicated
• If on antiretroviral therapy, must not be taking zidovudine or stavudine
• Patients must not be participating in any other clinical trial or taking any other experimental medications within 14 days prior to registration

• Man or woman greater than or equal to (>=) 18 years of age
• In Part 1, diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria
• International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS
• Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
• Participant has received an investigational drug or used an invasive investigational medical device within 30 days prior to Study Entry or is currently enrolled in an investigational study
• Prior treatment with imetelstat
• Have received corticosteroids greater than (>) 30 milligram per day (mg/day) prednisone or equivalent, or growth factor treatment within 4 weeks prior to study entry
• a) Prior treatment with a hypomethylating agent (example [eg], azacitidine, decitabine); b) Prior treatment with lenalidomide; c) Has received an erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting ESAs)

Key 1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the time of study treatment initiation. 2. Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease. a. To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
• Early first relapse (< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
• First refractory bone marrow relapse occurring any time after original diagnosis after achieving a CR (ie, ≥1 failed attempt to induce a second remission) OR
• Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2 relapses) OR
• Failing to achieve a CR from original diagnosis after at least 1 induction attempt 3. Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment. 4. Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2, or for children<2 years of age, ≥ 50mL/min/1.73 m2. 5. Adequate liver function, defined as both of the following: 1. Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert Syndrome 2. Alanine aminotransferase (ALT) ≤ 5 × institutional ULN 6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤ 16 years old, respectively. Key 1. Known allergy to any of the drugs used in the study. (Subjects who have had a previous allergy to PEG-asparaginase are eligible and if able, may receive Erwinia asparaginase at the investigator's discretion.) 2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) 3. Left ventricular fractional shortening < 30% 4. History of ≥ Grade 2 pancreatitis 5. Active graft‑versus‑host disease requiring systemic treatment 6. Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment 7. Down Syndrome 8. Prior therapy restrictions: 1. Subjects must have completed therapy with granulocyte‑colony stimulating factor (G‑CSF) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered. 2. Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation. 3. Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before study treatment initiation. 4. At least 3 antibody half‑lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab, 69 days for epratuzumab and 36 days for inotuzumab) before subjects may initiate study treatment. 5. Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation 9. Hepatitis B infection with positive hepatitis B DNA

1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following: 1. Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or 2. Urinary M-protein excretion at least 200 mg/24 hours; or 3. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal. 2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen. 3. Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen. 4. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met: Best response achieved with prior bortezomib at any time was ≥ PR and with the last PI (PI therapy (alone or in combination) was ≥ PR, AND Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment. 5. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1. 6. Adequate hepatic function within 28 days prior to C1D1 7. Adequate renal function within 28 days prior to C1D1 8. Adequate hematopoietic function within 7 days prior to C1D1 1. Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor. 2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. 3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures. 4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1. 5. Active plasma cell leukemia. 6. Documented systemic light chain amyloidosis. 7. MM involving the central nervous system. 8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. 9. Spinal cord compression. 10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication 11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids. 12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including investigational therapies) ≤ 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. Patients on long-term glucocorticoids during Screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study. 13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1. 14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1. 15. Pregnant or breastfeeding females. 16. Body Surface Area < 1.4 m2 at baseline, calculated by the Dubois or Mosteller method. 17. Life expectancy of < 4 months. 18. Major surgery within 4 weeks prior to C1D1. 19. Active, unstable cardiovascular function: 1. Symptomatic ischemia, or 2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or 3. Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or 4. Myocardial infarction within 3 months prior to C1D1. 20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity 21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen. 22. Active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment. 23. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent. 24. Contraindication to any of the required concomitant drugs or supportive treatments. 25. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.

• Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
• A solid tumor diagnosis in the setting of:
• a) a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
• b) a documented NTRK fusion unresponsive to a prior TRK inhibitor
• c) a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
• NTRK gene fusions will be identified in a CLIA-certified (or equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on an ETV6+ FISH test without identifying NTRK3.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 2 in adults or Karnofsky Performance Score (KPS) Score≥50% (age ≥ 16 years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years).
• Life expectancy of at least 3 months.
• Adequate hematologic, hepatic and renal function.
• Patients with stable central nervous system (CNS) primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms have been stable for 7 days prior to the first dose of selitrectinib.
• Ability to receive study drug orally or by enteral administration
• Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib (TPX-0005)), taletrectinib (DS-6501b/AB-106)). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed.
• Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of grapefruit juice or Seville oranges, or drugs associated with QT prolongation.
• Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, or prolongation of QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6 months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection.
• Pregnancy or lactation.
• Known hypersensitivity to selitrectinib or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.

1. Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure; specifically able to comply with the PK assessment schedule during the first 2 treatment cycles. 2. Men or women ≥18 years who are candidates to receive IV decitabine according to FDA or European Medicines Agency (EMA) approved indications: 1. In North America: Participants with MDS previously treated or untreated with de novo or secondary MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia [CMML]), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, -2, or high-risk MDS. 2. In Europe: Participants with de novo or secondary AML, as defined by the World Health Organization (WHO) criteria, who are not candidates for standard induction chemotherapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 4. Adequate organ function defined as follows: 1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤2.5 × ULN. 2. Renal: serum creatinine ≤1.5 × ULN or calculated creatinine clearance or glomerular filtration rate >50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. 5. No major surgery within 30 days of first study treatment. 6. Life expectancy of at least 3 months. 7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause, defined as no menses for at least 1 year AND either age ≥65 years or follicle-stimulating hormone levels in the menopausal range. 8. Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method (eg, use of a condom AND diaphragm, with spermicide). 1. Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts. 2. Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection in the 30 days before screening. 3. Treatment with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment. 4. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment. 5. Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment.) 6. Poor medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the patient at risk of not being able to complete at least 2 cycles of treatment. 7. Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the subject to high risk of noncompliance with the protocol. 8. Rapidly progressive or highly proliferative disease (total white blood cell count of >15 × 10^9/L) or other criteria that render the subject at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months. 9. Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ASTX727, or compromise completion of the study or integrity of the study outcomes. 10. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 2 years.

• Willing to be registered into the pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program
• Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less than 120 days old
• Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or prostate cancer not requiring therapy
• High risk patients with relapsed refractory multiple myeloma (RRMM), who have:
• received at least one prior but no more than 3 prior therapies
• exposed to both a PI and an IMiD
• had early relapse after initial treatment Early relapse as defined by at least one of the following: (Relapse is defined as the IMWG uniform response) 1. Relapse within 3 years of initiation of induction chemo therapy for post autologous stem cell transplantation (ASCT) followed by maintenance, or 18 months if unmaintained after ASCT 2. Within 18 months of initial non-ASCT based therapy
• Patients must have progressed after their most recent treatment and require therapy for myeloma
• Females of reproductive potential must have a negative pregnancy test at baseline, be non-lactating, and willing to adhere to scheduled pregnancy testing
• Females of reproductive potential and males must practice and acceptable method of birth control
• Laboratory values obtained ≤ 14 days prior to registration:
• Absolute neutrophil count (ANC) ≥ 1000/ul
• Hemoglobin (Hgb) ≥ 8 g/dl
• Platelet (PLT) ≥ 75,000/ul
• Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL
• Aspartate aminotransferase (AST) <3 x ULN
• Creatinine Clearance ≥ 30 mL/min Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:
• Serum monoclonal protein ≥ 0.5 g by protein electrophoresis
• ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum immunoglobulin free light chain (FLC) ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio
• Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• Ability to take aspirin, warfarin, or low molecular weight heparin Sub-Protocol Refer to each respective Sub Protocol for additional inclusion criteria. Patients will be ineligible for this study if they meet any one of the following criteria:
• Aggressive multiple myeloma requiring immediate treatment as defined by:
• Lactate dehydrogenase (LDH) > 2 times ULN
• Presence of symptomatic extramedullary disease or central nervous system involvement
• Hypercalcemia >11.5 mg/dl
• Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma relapse
• Any neurological emergency related to myeloma
• Clinical symptoms of hyperviscosity related to monoclonal protein
• Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior diagnosis of cast nephropathy
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days of enrolment
• Known hypersensitivity or development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drug. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of the agents
• Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy
• Pregnant or breast-feeding females
• Serious medical or psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance, interfere in the completion of treatment per protocol, or follow-up evaluation
• Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV) infection
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes]
• Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)
• Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD)
• Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the investigational drug, whichever is longer
• Prior anticancer therapy within 14 days of initiation of protocol therapy (Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed
• Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
• Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
• Other co-morbidity, which would interfere with patient's ability to participate in trial or that confounds the ability to interpret data from the study Sub-Protocol Refer to each respective Sub Protocol for additional exclusion criteria.

• Patients must have had histologic verification of AML at original diagnosis
• Patient must have one of the following:
• Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.
• Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
• To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016)
• Relapsed patients
• Patients must be in first relapse, and
• Patients must not have received prior re-induction therapy
• Refractory patients
• Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example
• Treatment-related AML (t-AML)
• Patients must be previously untreated for secondary AML
• To be eligible for the phase 2 efficacy phase:
• Relapse patients:
• Patients must be in first marrow relapse, and
• Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
• Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
• Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, stem cell transplant or radiotherapy prior to entering this study; all prior treatment-related toxicities must have resolved to =< grade 2 prior to enrollment
• Myelosuppressive chemotherapy: must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (excluding hydroxyurea)
• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of CPX-351
• Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent such as steroids, retinoids; Note: for agents that have known adverse events occurring beyond 7 days after administration (i.e. monoclonal antibodies), this period must be extended beyond the time during which acute adverse events are known to occur
• Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation; Note: patients must have received =< than 13.6 Gray (Gy) prior radiation to the mediastinum
• Stem cell transplant (SCT): no evidence of active graft vs. host disease for at least 4 weeks; for allogeneic SCT patients, >= 3 months must have elapsed since transplant
• Must have received no more than 1 prior autologous or allogeneic stem cell transplant.
• Patients must be off all systemic immunosuppressive therapy for at least 2 weeks, excluding hydrocortisone for physiologic cortisol replacement
• Intrathecal cytotoxic therapy:
• No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
• At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
• Growth factors:
• Patients must not have received growth factors for 7 days prior to CPX-351
• Patients must not have received pegfilgrastim for 14 days prior to CPX-351
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (males and females)
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (males and females)
• Age 6 to < 10 years: maximum serum creatinine 1.0 mg/dL (males and females)
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (males and females)
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (males) and 1.4 mg/dL (females)
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
• Direct bilirubin < 1.5 x upper limit of normal (ULN) for age and institution
• Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x upper limit of normal (ULN) for age and institution (unless it is related to leukemic involvement)
• Shortening fraction of >= 27% by echocardiogram, or
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT (using Bazett's formula [QTcB]) interval < 500 msecs
• Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures are well controlled
• Central nervous system (CNS) toxicity =< grade 2
• Patients with a known history of human immunodeficiency virus (HIV) are eligible, if they meet all of the following conditions:
• No history of HIV complications with the exception of cluster of differentiation (CD)4 count < 200 cells/mm^3
• No antiretroviral therapy with overlapping toxicity such as myelosuppression
• HIV viral loads below the limit of detection
• No history of highly active antiretroviral therapy (HAART)-resistant HIV
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients who have received > 450 mg/m^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:
• Doxorubicin (doxorubicin hydrochloride): 1
• Mitoxantrone: 3
• Idarubicin: 3
• Epirubicin: 0.5
• Patients who are currently receiving another investigational drug
• Patients receiving medications for treatment of left ventricular systolic dysfunction
• Patients with any of the following diagnoses:
• Acute promyelocytic leukemia (APL)
• Down syndrome
• Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
• Wilson's disease and any other disorder of copper metabolism
• Juvenile myelomonocytic leukemia (JMML)
• Patients with documented active, uncontrolled infection at the time of study entry
• Patients with known active hepatitis B virus (HBV) and hepatitis C virus (HCV) infections
• Patients with prior allergy to daunorubicin and/or cytarabine
• Female patients who are pregnant are ineligible
• Lactating females are not eligible
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of chemotherapy

• INCLUSION CRITERIA: Patients must have one of the following histologic diagnoses: -Patients must have Burkitt Lymphoma. Effective with Amendment J (version date: 06/24/2014), the following histologies were removed as the maximum number allowed for these sub-groups has been reached: B-cell lymphoma: unclassifiable with features intermediate between Diffuse Large B cell lymphoma and Burkitt Lymphoma ; c-MYC + DLBCL and c-MYC+ plasmablastic lymphoma. If questions arise related to diagnosis, please contact the NCI Principal Investigator, Dr. Mark Roschewski or the NCI study coordinator, A. Nicole Lucas.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of EPOCH-R in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials
• Pathology confirmed by treating institution s Pathology Department.
• No prior treatment except patients may be entered if they have had prior limited-field radiotherapy, a short course of glucocorticoids, cyclophosphamide for an urgent problem at diagnosis (e.g. epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture.
• All disease stages.
• HIV negative or positive.
• HIV positive patients on antiretrovival therapy regimen must be willing to suspend all Highly Active Antiretroviral Therapy (HAART) except in circumstances described in section 6.5.
• ECOG 0-4
• Ability of patient or durable power of attorney (DPA) for healthcare to give informed consent.
• Hepatitis B + patients may be enrolled at the discretion of the investigator. EXCLUSION CRITERIA:
• Patients with Primary CNS Lymphoma.
• Inadequate renal function, defined as serum Cr > 1.5 or creatinine clearance < 50ml/min/1.73m2 unless lymphoma related.
• Inadequate hepatic or hematological function: as follows, unless lymphoma-/disease-related: bilirubin greater than 2 mg/dl (total) except greater than 5 mg/dl in patients with Gilbert s syndrome as defined by greater than 80% unconjugated, ANC less than 1000 and platelets less than 75,000.
• The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, female subject of child-bearing potential not willing to use an acceptable method of birth control(i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion will not be eligible to participate in the study.
• Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without child-bearing potential.
• The effects of EPOCH-R on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion, will not be eligible to participate in the study.
• History of a prior invasive malignancy in past 5 years.
• Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If echo is obtained the LVEF should exceed 40%.
• Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety.
• HIV positive patients with advanced immune supression and evidence of HIV resistant to all combinations of antiretroviral therapy considered at high risk of non lymphoma related death within 12-months due to other AIDS complications should not be enrolled on the study.

Inclusion Criteria (Induction):
• Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology
• Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., ≥ 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology
• Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy) required if the interval since tissue diagnosis of low-grade malignant lymphoma is > 24 months
• Bone marrow biopsy alone not acceptable
• Stage II, III, or IV AND grade 1, 2, or 3a disease
• Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:
• Patient must meet ≥ 1 of the following GELF criteria:
• Nodal or extranodal mass ≥ 7 cm
• At least 3 nodal masses > 3.0 cm in diameter
• Systemic symptoms due to lymphoma or B symptoms
• Splenomegaly with spleen > 16 cm by CT scan
• Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)
• Leukemic presentation (≥ 5.0 x 10^9/L malignant circulating follicular cells)
• Cytopenias (polymorphonuclear leukocytes < 1.0 X 10^9/L, hemoglobin < 10 g/dL, and/or platelets < 100 x 10^9/L)
• Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):
• Age ≥ 60 years
• Stage III-IV disease
• Hemoglobin level < 12 g/dL
• > 4 nodal areas
• Serum lactate dehydrogenase (LDH) level above normal
• At least 1 objective measurable disease parameter
• Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization
• Measurable disease in the liver is required if the liver is the only site of lymphoma
• HIV-positive patients must meet all of the following criteria:
• HIV is sensitive to antiretroviral therapy
• Must be willing to take effective antiretroviral therapy if indicated
• No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis
• No history of AIDS-defining conditions
• If on antiretroviral therapy, must not be taking zidovudine or stavudine
• Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and ≥ 2 months following completion of study therapy or until the CD4 cells recover to over 250 cells/mm³
• ECOG performance status 0-2
• Absolute neutrophil count (ANC) ≥ 1,500/mm³ (includes neutrophils and bands)
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 2.0 mg/dL
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 5 x upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 x ULN
• Total bilirubin ≤ 1.5 x ULN (patients with known Gilbert disease should contact the study PI)
• Negative pregnancy test
• Fertile patients must use 2 effective methods (1 highly effective and 1 additional effective method) of contraception ≥ 28 days before, during, and for ≥ 28 days after completing study treatment
• Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® (for patients randomized to arm C and proceed onto arm F) Exclusion Criteria (Induction):
• Prior chemotherapy, radiotherapy, or immunotherapy for lymphoma
• Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy
• A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed
• Recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for ≥ 2 years
• Pregnant or nursing
• Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
• ≥ grade 2 neuropathy
• Myocardial infarction within the past 6 months
• NYHA class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Known hypersensitivity to boron or mannitol
• Chronic carriers of hepatitis B virus (HBV) with positive hepatitis surface antigen (HBsAg +) Inclusion Criteria (Continuation):
• Patient must have improved their response or have had no interval change in their tumor measurements with restaging from Induction cycle 3 to 6 as determined at Cycle 6 restaging.
• Adequate organ function
• ECOG performance status 0-2
• Patients with a prior history of HBV infection, but immune, with only IgG hepatitis core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine 100 mg po daily) for ≥ 1 week prior to course 1 and throughout induction and continuation therapy and for ≥ 12 months after the last rituximab dose
• Additional requirements for Arm C induction patients registering to arm F:
• Patients must be willing to take deep vein thrombosis (DVT) prophylaxis. Subjects with a history of a thrombotic vascular event will be required to have full anticoagulation, therapeutic doses of low molecular weight heparin or warfarin to maintain an INR between 2.0
•3.0, or any other accepted full anticoagulation regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with appropriate monitoring for that agent. Subjects without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Subjects who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen.
• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study/lenalidomide: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 28 days after discontinuation/stopping lenalidomide. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.
• Patient must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment.
• All males, regardless of whether they have undergone a successful vasectomy, must agree to use a latex condom during sexual contact with a female of childbearing potential, or to practice complete abstinence from heterosexual intercourse with any female of childbearing potential during the cycles of continuation therapy of which lenalidomide are taken and for at least 28 days after discontinuation/stopping lenalidomide. Patient must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment.
• Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® Exclusion Criteria (Continuation):
• Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)
• ≥ grade 2 neuropathy
• Additional requirements for Arm C induction patients registering to arm F:
• Not pregnant or breast-feeding

1. Intrauterine pregnancy 2. Age ≥ 18 3. Gestation age ≥ 37 weeks 0 days 4. Scheduled cesarean delivery 5. Second or third cesarean delivery 6. Singleton pregnancy 1. First cesarean delivery 2. Four or more cesarean deliveries 3. Intrauterine fetal death 4. Fetal anomalies 5. Documented coagulopathy (Elevated Prothrombin Time (PT), Elevated Partial Thromboplastin Time (PTT), Elevated International Normalized Ratio (INR)) 6. Thrombocytopenia (Platelet count < 100k) 7. Internal bleeding, external bleeding, easy bruising 8. History of thrombotic event 9. Hypertension 10. Diagnosis of renal insufficiency (Creatinine> 1 mg/dL) 11. Insulin-treated diabetes 12. Suspected morbidly adherent placenta 13. Placenta previa 14. Multiple Gestations 15. BMI ≥ 50 16. Hematocrit ≤ 25 17. Blood transfusion within 24 hours prior to cesarean delivery 18. History of abnormal bleeding or blood disorder 19. Planned general anesthesia

• Signed informed consent given by the subject or the subject's parent/legal guardian for those under 18 years of age or the age of consent by local regulation.
• Male and female subjects with a suspected or confirmed UCD diagnosis of any subtype, except NAGS deficiency.
• Suspected diagnosis is defined as having experienced a HAC or a documented high ammonia of >=100 µmol/L
• Confirmed diagnosis is determined via enzymatic, biochemical, or genetic testing.
• Requires nitrogen-binding agents according to the judgment of the Investigator
• Birth and older.
• All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception from signing the informed consent throughout the study and for 30 days after the last dose of study drug. Acceptable forms of contraception are (oral, injected, implanted or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.
• Subject has received chronic treatment with an oral phenylbutyrate (RAVICTI, NaPBA, Pheburane, or other) longer than 14 consecutive days within one year prior to enrollment.
• Temporary use of NaPBA for acute management of a hyperammonemic crisis in the past is acceptable.
• Any concomitant illness (e.g., malabsorption or clinically significant liver or bowel disease) which would preclude the subject's safe participation, as judged by the Investigator.
• Has undergone liver transplantation, including hepatocellular transplant.
• Subjects on NaBz at Baseline will be excluded if they are viewed by the Investigator as being unable to undergo NaBz transition to a PAA prodrug during the Initial Treatment Period.
• Known hypersensitivity to PBA or any excipients of the NaPBA/PBA formulations.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed at the Baseline Visit prior to the start of study drug.

Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF) 2. Subject has measurable disease, defined as:
• M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio 3. Subjects with one of the following cohort specific requirements: Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
• Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
• Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
• Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
• Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
• Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
• Subject must have the following HR factors:
•R-ISS stage III AND
• Early relapse defined as: Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance. Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance. 4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy The presence of any of the following will exclude a subject from enrollment: 1. Subject used any investigational agents within 14 days of leukapheresis 2. Subject received any of the following within the last 14 days of leukapheresis: 1. Plasmapheresis 2. Major surgery (as defined by the investigator) 3. Radiation therapy other than local therapy for myeloma associated bone lesions 4. Use of any systemic anti-myeloma drug therapy 3. Subject with known central nervous system involvement with myeloma 4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation 5. History or presence of clinically relevant central nervous system (CNS) pathology 6. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis 7. Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment 8. Ongoing treatment with chronic immunosuppressants 9. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy 10. Subject has received ASCT within 12 weeks prior to leukapheresis 11. Subject has history of primary immunodeficiency 12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C 13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment 14. Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years 15. Pregnant or lactating women 16. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab