Oral AMXT 1501 Dicaprate in Combination With IV DFMO

Exclusion Criteria

• •Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy: The following minimum periods from treatment apply:
• •* (a) Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
• •* (b) Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting growth factor.
• •* (c) Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• •* (d) Immunotherapy: At least 42 days after the completion of any type of vaccination.
• •* (e) Monoclonal antibodies: \>21 days must have elapsed from the infusion of last dose of antibody and toxicity related to antibody therapy must be recovered to Grade ≤1.
• •* (f) Radiation therapy: Patients must have had their last fraction of craniospinal or focal irradiation a minimum of 8-12 weeks prior to enrollment.
• •Patient is able to take oral medications and willing to use an at-home infusion pump.
• •Must have adequate bone marrow and renal/hepatic function at the screening and baseline visits, defined as:
• •* (a) Absolute neutrophil count (ANC) ≥1.5×109/L without granulocyte colony-stimulating factor (G-CSF) support within 7 days
• •* (b) Platelet ≥100×109/L, without transfusion within 7 days
• •* (c) Hemoglobin ≥9 g/dL, without transfusion support within 7 days
• •* (d) Activated partial thromboplastin time/ partial thromboplastin time (aPTT/PTT) ≤1.5×ULN.
• •* (e) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (if liver metastases are present, then ≤5×ULN is allowed).
• •* (f) Total serum bilirubin ≤1.5×ULN, (except for patients with known Gilbert's Syndrome in whom ≤3×ULN is permitted).
• •* (g) The patient is clinically euthyroid.
• •* (h) Renal: Serum creatinine \<1.5×ULN or creatinine clearance ≥60 mL/min/1.73 m2 for patients with serum creatinine levels \>1.5×ULN.
• •* (i) Any Grade 3 or higher lab abnormalities should be discussed and approved by the Medical Monitor prior to enrollment (even if not considered clinically significant).
• •Active secondary malignancies will not be allowed, with the exception of:
• •* (a) Adequately treated basal cell carcinoma, SCC of the skin, or in situ cervical cancer;
• •* (b) Adequately treated Stage 1 cancer from which the subject is currently in remission and has been in remission for ≥2 years;
• •* (c) Low-risk prostate cancer with Gleason score \<7 and prostate-specific antigen \<10 ng/mL, or
• •* (d) Any other cancer from which the patient has been disease-free for ≥3 years.
• •Patient compliance and geographic proximity (as determined by the Principal Investigator \[PI\]) to allow adequate follow-up.
• •Both male and female patients must be willing to consent to using highly effective contraception prior to study entry, while on treatment, and at least 3 months thereafter
• •Please note different criteria for patients with Advanced Solid Tumors (adults) vs patients with DIPG or DMG (pediatric)
• •EXCLUSION FOR PATIENTS DIAGNOSED WITH ADVANCED SOLID TUMOR(S)
• •Have a seizure disorder where \>1 seizure has occurred within the last year.
• •Patient with treated (surgically excised or irradiated) with stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and baseline brain CT with contrast or magnetic resonance imaging (MRI) within 2 weeks of initiation of study drug is negative for new brain metastases. Patients with stable brain metastases must not require therapy with corticosteroids.
• •Treatment with radiation therapy, surgery, chemotherapy, or immunotherapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C). Limited prior palliative radiation may be permissible no less than 2 weeks prior to C1D1 with approval from the Medical Monitor.
• •EXCLUSION FOR PATIENTS WITH DIPG OR DMG
• •\- Patients with seizure disorders may be enrolled if seizures are well-controlled, defined as no increase in seizure frequency in the prior 7 days.
• •Anticonvulsants should be used as clinically indicated.
• •The use of enzyme inducing anticonvulsants is not permitted.
• •EXCLUSION FOR ALL PATIENTS
• •Have clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 3 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, or history of cerebrovascular accident \[CVA\]) within 6 months of enrollment.
• •History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful.
• •* Screening QTcF interval \>480 ms is excluded. In the event that a single QTcF is \>480 ms, the patient may enroll if the average QTcF for the 3 ECGs is \<480 ms.
• •* For patients with an intraventricular conduction delay (QRS interval \>120 ms), the JTc interval may be used in place of the QTcF with Sponsor approval. The JTc must be \<340 ms if JTc is used in place of the QTcF.
• •* Patients with an intraventricular delay due to a left bundle branch block are excluded.
• •Note: QTcF prolongation due to pacemaker may enroll if the JTc is normal
• •Had major surgery, other than diagnostic surgery, within 4-weeks prior to Day 1.
• •Have active bacterial, viral, or fungal infections requiring systemic therapy.
• •Women who are pregnant or lactating: NOTE: Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 1 week prior to treatment.
• •* Women not OCBP is defined as
• •* (i) Postmenopausal with \>1 year since last menses
• •* \-- (a) If \<65 years old, follicle-stimulating hormone (FSH) \>40 mIU/mL.
• •* \-- (b) If ≥65 years old and not on hormone replacement therapy (HRT), FSH \>30 mIU/mL.
• •* \-- (c)If ≥65 years old and on HRT, the FSH requirement is not applicable. Postmenopausal females on HRT will be allowed if HRT has been stable for ≥6 months prior to dosing of study drug(s).
• •* Written medical documentation of being sterilized (e.g., hysterectomy, double oophorectomy, bilateral salpingectomy) with the procedure performed ≥6 months prior to dosing study drug(s).
• •Note: Tubal ligation is not considered a form of permanent sterilization.
• •Patients may not have any unresolved toxicity \>Grade 1 from previous anticancer therapy, except for stable chronic toxicities that are not expected to resolve (i.e., peripheral neuropathy, alopecia, etc.). Patients who have an ongoing requirement for thyroid replacement therapy from prior exposure to a checkpoint inhibitor but who are clinically euthyroid are permitted.
• •Have an unwillingness or inability to comply with procedures required in this protocol.