Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma

Exclusion Criteria

• •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
• •Pregnancy or Breast-Feeding
• •Concomitant Medications:
• •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.