Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors

Inclusion Criteria:

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

• PART B: Patients must be >= 12 months and =< 30 years of age at the time of studyenrollment

• Patients with recurrent or refractory solid tumors including non-Hodgkin lymphomaand desmoid tumors are eligible. Patients must have had histologic verification ofmalignancy at original diagnosis or relapse

• PART A: Patients with relapsed or refractory solid tumors, including patients withnon-Hodgkin lymphoma and desmoid tumors

• PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors,osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors withWnt pathway aberrations. For the Wnt pathway aberrations cohort we will include themost common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I,G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in theAPC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in theGSK3B, LRP6, and LGR5 genes. For patients without prior sequencing,immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-cateninstaining will be accepted for the following tumor types: colorectal carcinoma,melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma,pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas

• PART A: Patients must have either measurable or evaluable disease. For desmoidtumors, the patient must have disease that the investigator deems unresectable orsufficiently morbid or potentially life-threatening that there is favorablerisk/benefit to the patient to participate in the trial

• PART B: Patients must have measurable disease. For desmoid tumors, the patient musthave measurable disease that the investigator deems unresectable or sufficientlymorbid or potentially life-threatening that there is favorable risk/benefit to thepatient to participate in the trial

• Patients must have a performance status corresponding to Eastern CooperativeOncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years ofage and Lansky for patients =< 16 years of age

• 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 be myelosuppressive

• Solid tumor patients: >= 21 days after the last dose of myelosuppressivechemotherapy (42 days if prior nitrosourea)

• Non-Hodgkin lymphoma patients

• A waiting period prior to enrollment is not required for patientsreceiving standard maintenance chemotherapy (i.e., corticosteroid,vincristine, thioguanine [6MP], and/or methotrexate)

• >= 14 days must have elapsed after the completion of other cytotoxictherapy, with the exception of hydroxyurea, for patients notreceiving standard maintenance therapy

• NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hoursprior to the start of protocol therapy

• Anti-cancer agents not known to be myelosuppressive (e.g., not associated withreduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the lastdose 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 agents 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

• 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.).

• External beam radiation therapy (XRT)/external beam irradiation includingprotons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT orif radiation to >= 50% of the pelvis; >= 42 days if other substantial bonemarrow (BM) radiation

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

• Patients must not have received prior exposure to tegavivint

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheralabsolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusionsfor at least 7 days prior to enrollment) (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin >= 8.0g/dL at baseline (may receive red blood cell [RBC] transfusions) (within 7 daysprior to enrollment)

• Patients with known bone marrow metastatic disease will be eligible for studyprovided they meet blood counts (may receive transfusions provided they are notknown to be refractory to red cell or platelet transfusions). These patients willnot be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patientsmust be evaluable for hematologic toxicity for the dose-escalation part of thestudy. If dose-limiting hematologic toxicity is observed, all subsequent patientsenrolled on Part A must be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 or a creatinine based on age/gender as follows (within 7 days priorto enrollment):

• Age; maximum serum creatinine

• Age 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)

• Age 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)

• Age 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)

• Age 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)

• Age 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)

• Age >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)

• PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanineaminotransferase [ALT]) =< 135 U/L. For the purpose of this study, the ULN for SGPTis 45 U/L (within 7 days prior to enrollment)

• PATIENTS WITH SOLID TUMORS: Albumin >= 2 g/dL (within 7 days prior to enrollment)

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study because there isyet no available information regarding human fetal or teratogenic toxicities.Pregnancy tests must be obtained in girls who are post-menarchal. Males or femalesof reproductive potential may not participate unless they have agreed to use twoeffective methods of birth control, including a medically accepted barrier orcontraceptive method (e.g., male or female condom) for the duration of the study.Abstinence is an acceptable method of birth control

• 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 inhibitors ofCYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoidedfrom 14 days prior to the 1st dose of tegavivint to the end of the study

• Patients who have received bisphosphonates within 4 weeks prior to study enrollmentwill be excluded

• Patients who have received denosumab within 180 days prior to study enrollment willbe excluded

• Patients with primary brain tumors are ineligible

• Patients with known central nervous system (CNS) metastasis, except forcraniopharyngeal tumors, will be excluded

• Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget'sdisease, osteomalacia) are not eligible

• Patients with a disorder associated with abnormal bone metabolism will be excluded

• Patients with grade >= 2 hypocalcemia that is not corrected with oral calciumsupplementation will be excluded

• Patients with vitamin D < 20 ng/mL will require supplementation, or will otherwisebe excluded. Patients must agree to take vitamin D +/- calcium supplements (ifnecessary) according to institutional or published guidelines. Additional calciumsupplementation is not required if adequate dietary intake can be ascertained

• Patients with pre-existing grade 3 osteoporosis are excluded

• 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