Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma

Inclusion Criteria: Diagnosis: Participants must have had histologic verification of osteosarcoma at original diagnosis or relapse. * All participants with relapsed or refractory osteosarcoma are eligible, provided they received front-line treatment with a regimen that contained at least 3 of the following agents: methotrexate, doxorubicin, cisplatin, and ifosfamide -Disease Status: * Dose Escalation: Participants must have either measurable or evaluable disease per RECIST.Note: Participants with no evidence of disease on imaging (e.g., following pulmonary metastasectomy) are not eligible during the dose escalation phase. * Dose Expansion: Participants with measurable or evaluable disease per RECIST and those with no evidence of disease on imaging following pulmonary metastasectomy are eligible during the dose expansion phase. -Performance Level: Participants must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60, or Eastern Cooperative Oncology Group (ECOG) ≤ 2 Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory to assess the performance score. -Prior Therapy: Participants must have fully recovered from the clinically significant acute effects of all prior anti-cancer chemotherapy, immunotherapy, surgery, or radiation therapy before enrollment. * Myelosuppressive chemotherapy: ≥ 14 days after the last dose. * Hematopoietic growth factors: ≥ 14 days after a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for a short-acting growth factor. For agents with known delayed adverse events, extend recovery period accordingly. * Biologic (anti-neoplastic) agent: ≥ 7 days after the last dose. Extend period if adverse events occur beyond 7 days. * Cellular therapy: ≥ 21 days since last dose (e.g., modified T cells, gamma-delta T cells, natural killer (NK) cells, dendritic cells) with recovery from associated toxicities. * Interleukins, interferons, and cytokines (excluding hematopoietic growth factors): ≥ 21 days since last dose. * Antibodies: 7 days or 3 half-lives (whichever is longer), up to 30 days. Toxicity must be resolved to Grade ≤ 1. * Radiation therapy (XRT): * 14 days after local palliative XRT (small port) * 150 days after radiation to ≥ 50% of pelvis or bone marrow * 6 weeks after substantial bone marrow radiation Prior use of Nucleoside Analogue (Gemcitabine): Allowed. Investigational agents not otherwise specified: ≥ 30 days since last dose. Surgery: ≥ 2 weeks since last major surgery, including pulmonary metastasectomy (central line placement and core/small open biopsies are excluded) Organ Function Requirements: * Adequate Bone Marrow Function Defined As: * Peripheral absolute neutrophil count (ANC) ≥ 750/mm3 (0.75x109/L) * Platelet count ≥ 75,000/mm3 (75x109/L) * Adequate Renal Function Defined As: Creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73 m2 * Adequate Liver Function Defined As: * Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x the upper limit of normal (ULN) for age * ALT ≤ 5 x the ULN * Adequate Pulmonary Function Defined As: No dyspnea at rest, no exercise intolerance, and no oxygen requirement (pulse oximetry \> 93% on room air). * Adequate Cardiac Function Defined As: QTc ≤ 470 ms using Fridericia formula Exclusion Criteria: * CNS disease: Patients with a history of intraparenchymal CNS disease (osteosarcoma) are not eligible unless they have imaging documenting stability of CNS lesions for ≥ 3 months prior to enrollment * Pregnancy or Breast-Feeding * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained * Males or females of reproductive potential are not eligible unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method * Concomitant Medications: * Investigational Drugs: Subjects who are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents are not eligible. * CYP3A4/5 Agents: Patients currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days before the 1st dose of tegavivint to the end of the study. See Appendix II for a list of agents. * Bisphosphonates: Patients receiving bisphosphonates within 4 Weeks of study enrollment are not eligible. * Denosumab: Patients who have received denosumab within 180 days prior to study enrollment are not eligible * Infection: Subjects who have an active, uncontrolled infection. * Subjects who have received prior solid organ or allogeneic stem cell transplantation. * Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. * Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia). * Patients with a disorder associated with abnormal bone metabolism. * Patients with ≥ 2 grade hypocalcemia that is not corrected with oral calcium supplementation. * Patients with vitamin D \< 20 ng/mL will require supplementation or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained. * Patients who have previously received tegavivint are not eligible.