Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

Inclusion Criteria:

• Patient must have enrolled onto APEC1621SC and must have been given a treatmentassignment to MATCH to APEC1621K based on the presence of an actionable mutation asdefined in APEC1621SC

• Patients must be >= than 12 months and =< 21 years of age at the time of studyenrollment

• Patients must have a body surface area >= 0.78 m^2 at enrollment

• Patients must be able to swallow intact tablets

• Patients must have radiographically measurable disease at the time of studyenrollment. Patients with neuroblastoma who do not have measurable disease but havemetaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable diseasein patients with CNS involvement is defined as any lesion that is at minimum 10 mmin one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)

• Note: The following do not qualify as measurable disease:

• Malignant fluid collections (e.g., ascites, pleural effusions)

• Bone marrow infiltration except that detected by MIBG scan forneuroblastoma

• Lesions only detected by nuclear medicine studies (e.g., bone, gallium orpositron emission tomography [PET] scans) except as noted forneuroblastoma

• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

• Previously radiated lesions that have not demonstrated clear progressionpost radiation

• Leptomeningeal lesions that do not meet the measurement requirements forResponse Evaluation Criteria in Solid Tumors (RECIST) 1.1.

• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16years of age. Note: Neurologic deficits in patients with CNS tumors must have beenrelatively stable for at least 7 days prior to study enrollment. Patients who areunable to walk because of paralysis, but who are up in a wheelchair, will beconsidered ambulatory for the purpose of assessing the performance score.

• Patients must have fully recovered from the acute toxic effects of all prioranti-cancer therapy and must meet the following minimum duration from prioranti-cancer directed therapy prior to enrollment. If after the required timeframe,the numerical eligibility criteria are met, e.g. blood count criteria, the patientis considered to have recovered adequately

• Cytotoxic chemotherapy or other anti-cancer agents known to bemyelosuppressive. >= 21 days after the last dose of cytotoxic ormyelosuppressive chemotherapy (42 days if prior nitrosourea)

• Anti-cancer agents not known to be myelosuppressive (e.g. not associated withreduced platelet or absolute neutrophil count [ANC] counts): >= 7 days afterthe last dose of agent

• Antibodies: >= 21 days must have elapsed from infusion of last dose ofantibody, and toxicity related to prior antibody therapy must be recovered tograde =< 1

• Corticosteroids: If used to modify immune adverse events related to priortherapy, >= 14 days must have elapsed since last dose of corticosteroid

• Hematopoietic growth factors: >= 14 days after the last dose of a long-actinggrowth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor.For growth factors that have known adverse events occurring beyond 7 days afteradministration, this period must be extended beyond the time during whichadverse events are known to occur. The duration of this interval must bediscussed with the study chair and the study-assigned research coordinator

• Interleukins, interferons and cytokines (other than hematopoietic growthfactors): >= 21 days after the completion of interleukins, interferon orcytokines (other than hematopoietic growth factors)

• Stem cell infusions (with or without total body irradiation [TBI]):

• Allogeneic (non-autologous) bone marrow or stem cell transplant, or anystem cell infusion including donor lymphocyte infusion (DLI) or boostinfusion: >= 84 days after infusion and no evidence of graft versus hostdisease (GVHD)

• Autologous stem cell infusion including boost infusion: >= 42 days

• Cellular Therapy: >= 42 days after the completion of any type of cellulartherapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells,etc.)

• Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 daysafter local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

• Note: Radiation may not be delivered to "measurable disease" tumor site(s)being used to follow response to subprotocol treatment

• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42days after systemically administered radiopharmaceutical therapy

• Patients must not have received prior exposure to AG-120 (ivosidenib) or otherIDH1 inhibitors

• For patients with solid tumors without known bone marrow involvement: Peripheralabsolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)

• For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelettransfusions for at least 7 days prior to enrollment)

• Patients with known bone marrow metastatic disease will be eligible for studyprovided they meet the blood count (may receive transfusions provided they are notknown to be refractory to red cell or platelet transfusions). These patients willnot be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 (within 7 days prior to enrollment), or

• A serum creatinine based on age/gender (within 7 days prior to enrollment)

• Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6

• Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8

• Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1

• Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2

• Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4

• Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4

• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN)for age (within 7 days prior to enrollment)

• Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 daysprior to enrollment)

• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)

• Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment)

• Note: Patients should avoid concomitant medication known or suspected toprolong QTc interval or cause Torsades de Pointes. Patients who are receivingdrugs that prolong the QTc are eligible if the drug is necessary and noalternatives are available

• Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled

• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]version [v]5.0) resulting from prior therapy must be =< grade 2, with the exceptionof decreased tendon reflex (DTR). Any grade of DTR is eligible

• All patients and/or their parents or legally authorized representatives must sign awritten informed consent. Assent, when appropriate, will be obtained according toinstitutional guidelines

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risksbecause there is yet no available information regarding human fetal or teratogenictoxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Malesor females of reproductive potential may not participate unless they have agreed touse an effective non-hormonal contraceptive method for the duration of studytreatment and for at least 1 month after last dose of AG-120 (ivosidenib). SinceAG-120 (ivosidenib) may decrease concentrations of hormonal contraceptives, hormonalcontraceptives are not considered effective contraception when co-administered withAG-120 (ivosidenib)

• Patients receiving corticosteroids who have not been on a stable or decreasing doseof corticosteroid for at least 7 days prior to enrollment are not eligible. If usedto modify immune adverse events related to prior therapy, >= 14 days must haveelapsed since last dose of corticosteroid

• Patients who are currently receiving another investigational drug are not eligible

• Patients who are currently receiving other anti-cancer agents are not eligible

• Patients who are receiving cyclosporine, tacrolimus or other agents to preventgraft-versus-host disease post bone marrow transplant are not eligible for thistrial

• Patients who are currently receiving drugs that are strong inducers or moderate tostrong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to stronginhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the endof the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNStumors or metastases, on a stable dose, are allowed. In addition, patients receivingsensitive or narrow therapeutic range substrates of CYP3A4 are not eligible

• Patients with a history of progressive multifocal leukoencephalopathy are noteligible

• Patients who have an uncontrolled infection are not eligible

• Patients who have received a prior solid organ transplantation are not eligible

• Patients who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study are not eligible