A Study of Deferoxamine (DFO) in People With Leptomeningeal Metastasis

Inclusion Criteria:

• Age ≥ 18 years on the day of consenting to study

• ECOG performance status ≤ 2 or KPS ≥ 60.

• Life expectancy ≥ 8 weeks in the opinion of the Investigator

• LM from any solid tumor malignancy (1a and 1b), that is either:

• Newly diagnosed: As evidenced by positive CSF cytology, CTC count >3.0/3.0 mL,or unequivocal radiographic evidence of LM on contrast-enhanced MRI, OR

• Recurrent: As evidenced by unequivocal radiographic progression oncontrast-enhanced MRI, the development of newly or recurrently positive CSFcytology, or a clinically-relevant rise in CSF CTCs at the discretion of thetreating Investigator. There are no restrictions on the number of recurrences.

OR

• Persistent: As evidenced by any detectable disease (abnormal leptomeningealenhancement on contrast-enhanced MRI; positive, suspicious, or atypical cytology;positive CSF CTCs; extrinsic cells on CSF cell count differential; or clinicalsymptoms attributed to LM) after receiving LM-directed radiation or systemictherapy. This includes patients with stable or partially responding LM who, in theopinion of the investigator, would benefit from additional LM-directed therapy.

• Confirmation of solid tumor malignancy (phase 1a and 1b) may be made byhistopathologic criteria of any primary or metastatic site. For patients thathave not previously undergone internal pathology review at MSKCC, a pathologyreport confirming the primary malignancy is sufficient.

• Patients can have concomitant parenchymal brain metastases at study entry aslong as they do not require active treatment or have been previously treated.

• Patients with seizure disorders, stable on appropriate antiepileptic therapies,are eligible for this trial.

• Patients must have normal CSF flow dynamics at the clinical judgment of thetreating investigator, with no obstructive hydrocephalus orventriculoperitoneal (VP) or ventriculoatrial (VA) shunt.

• Patients with isolated intracranial LM progression and stable extracranialdisease may enroll on trial. If this population is receiving systemic treatmentthat is controlling their extracranial disease, they may remain on this regimenduring study enrollment provided their LM progression occurred on this regimen.

• For patients with both intracranial and extracranial disease progression at thetime of study screening, necessitating change to their systemic tumor-directedtherapy:

• If the new systemic treatment of choice has known CNS activity at the discretion ofthe Principal Investigator, then they should be monitored on this new regimen for 21days with confirmation of persistent LM (by neuraxial imaging and CSF reassessment)before enrolling on study.

• If the new systemic treatment of choice has no known CNS activity at the discretionof the Principal Investigator, then they may start IT-DFO concurrently with the newsystemic treatment.

• Examples of systemic CNS-active treatments include but are not limited to:bevacizumab, temozolomide, carmustine, lomustine, etoposide, carboplatin, cisplatin,pemetrexed, doxorubicin, high-dose erlotinib, osimertinib, lorlatinib, lapatinib,tucatinib, capecitabine, dabrafenib, trametinib, vemurafenib, cobimetinib,ipilimumab, nivolumab, pembrolizumab, atezolizumab

• Patients must have a functioning Ommaya reservoir prior to the first IT-DFOadministration or be an appropriate surgical candidate for Ommaya reservoirplacement and agree to Ommaya reservoir placement as standard of care prior tothe first IT-DFO administration.

• Patients that have screening laboratory values out of range, but not clinicallysignificant, may be considered eligible on a case by case basis deemed by theclinical investigator. Adequate bone marrow and organ function is demonstratedby:

• White blood cell (WBC) count ≥ 2.5 K/mcL or if this value is less, an exemption hasbeen granted by the treating physician or primary investigator.

• Absolute neutrophil count (ANC) ≥ 1.0 K/mcL

• Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion, or if thisvalue is less, an exemption has been granted by the treating physician or primaryinvestigator.

• Hemoglobin (Hgb) ≥ 8 g/dL, or if this value is less, an exemption has been grantedby the treating physician or primary investigator.

• Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or if this value ismore, an exemption has been granted by the treating physician or primaryinvestigator.

• Serum bilirubin ≤ 1.5 times the ULN; or total bilirubin ≤ 3 times the ULN withdirect bilirubin within the normal range in patients with well documented GilbertDisease or if this value is more, an exemption has been granted by the treatingphysician or primary investigator.

• Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) ≤ 3 timesthe ULN, unless known hepatic disease wherein may be ≤ 5 times the ULN isacceptable. If this value is more, an exemption must be granted by the treatingphysician or primary investigator.

• Women of child-bearing potential and sexually active males must commit to theuse of effective contraception while on study.

Exclusion Criteria:

• Any CNS-directed irradiation within 7 days of first dose of IT-DFO.

• Patients receiving other therapy (either intrathecal or systemic) designed to treattheir LM, with ongoing acceptable control of their LM.

• Any contraindication to gadolinium-enhanced MRI

• Use of any systemic iron chelators within 4 weeks of first dose

• Use of ascorbic acid or prochlorperazine within 2 weeks of first dose

• Patients are not allowed to receive whole-brain radiation therapy or craniospinalradiation therapy during study enrollment.

• Patients must not have any physical and/or psychiatric illness that would interferewith their compliance and ability to tolerate treatment as per the protocol.

• Women may not be pregnant or breastfeeding

• Known hypersensitivity orSpecial Characters